Flame Retardant Alternatives
Tris(1,3-dichloro-2-propyl) Phosphate
Hazard Review
3-1
Tris(1,3-dichloro-2-propyl) phosphate:
Existing Data Summary Table ?Human Health Endpoints
T= Endpoint characterized by existing data * = Data available but not adequate Y = Endpoint not applicable
As noted in this key, a check mark indicates that an endpoint was adequately characterized by existing studies. It
does not indicate a positive or negative result for that particular endpoint.
Acute Toxicity Developmental Neurotoxicity
Toxicity
T T
Oral Acute and 28-day
delayed neurotoxicity
Reproduction/
T
Dermal of organophosphorus
developmental toxicity
substances (hen)
screen
Inhalation *
Neurotoxicity
Combined repeated
T
Eye irritation
screening battery
dose with reproduction/
(adult)
T developmental toxicity
Dermal irritation
screen
Developmental *
T
Skin sensitization
T neurotoxicity
Prenatal developmental
Subchronic Toxicity
Y
Additional
Chronic Toxicity
neurotoxicity studies
28-Day oral
Chronic toxicity (two
Immunotoxicity
90-Day oral * species)
T Immunotoxicity *
Combined repeated Combined chronic
dose with reproduction/ toxicity/
Genotoxicity
developmental toxicity carcinogenicity
screen
T
Gene mutation in vitro
Carcinogenicity
21/28-Day dermal
T
Gene mutation in vivo
Carcinogenicity (rat
90-Day dermal and mouse)
T
Chromosomal
aberrations in vitro
T
90-Day inhalation Combined chronic
toxicity/
Chromosomal *
Reproductive carcinogenicity
aberrations in vivo
Toxicity
T
DNA damage and
Reproduction/
repair
developmental toxicity
screen Other
Combined repeated
dose with reproduction/
developmental toxicity
screen
Reproduction and *
fertility effects
3-2
Tris(1,3-dichloro-2-propyl) phosphate:
Existing Data Summary Table ?Properties, Fate, and Ecotoxicity
T= Endpoint characterized by existing data * = Data available but not adequate Y = Endpoint not applicable
As noted in this key, a check mark indicates that an endpoint was adequately characterized by existing studies. It
does not indicate a positive or negative result for that particular endpoint.
P/Chem Properties Environmental Fate Ecotoxicity
T
Water solubility Bioconcentration Aquatic Toxicity
T T
Octanol/water partition Fish Fish acute LC50 *
coefficient
Daphnids Daphnia acute EC50 *
Oxidation/reduction
Green algae Mysid shrimp acute
T
Melting point LC50
Oysters
T
Boiling point Green algae EC50, *
Earthworms NOAEC, LOAEC
Vapor pressure *
Metabolism in fish * Fish chronic NOAEC,
T
Odor LOAEC
Degradation and
Oxidation/reduction Transport Daphnia chronic
chemical NOAEC, LOAEC
incompatibility Photolysis, atmosphere
Mysid shrimp chronic
T
Flammability Photolysis, water NOAEC, LOAEC
Explosivity Photolysis in soil Terrestrial
Organism Toxicity
T
Corrosion Aerobic biodegradation
characteristics
Bird LD50 (two
Anaerobic
Y species)
pH biodegradation
T Bird LC50 (two
UV/visible absorption Porous pot test
species)
T
Viscosity Pyrolysis *
Bird reproduction
T T
Density/relative Hydrolysis as a
Earthworm subchronic *
density/bulk density function of pH
EC50, LC50, NOAEC,
Y
Dissociation constant in LOAEC
Sediment/water
water biodegradation
Henry's Law constant Soil biodegradation w/
product identification
Indirect photolysis in
water
Sediment/soil
adsorption/desorption
3-3
Chemical Identity
2-Propanol, 1,3-dichloro-, phosphate (3:1)
CAS 13674-87-8
MF C9H15Cl6O4P
MW 430.91
SMILES ClCC(CCl)OP(=O)(OC(CCl)CCl)OC(CCl)CCl
Synonyms Tris(1,3-dichloro-2-propyl) phosphate, TDCPP, Fyrol FR-2
Human Health Endpoints
ACUTE TOXICITY
Acute Oral Toxicity (OPPTS Harmonized Guideline 870.1100; OECD Guidelines 425, 420,
423, 401).
Conclusion:
The available acute oral toxicity data were judged adequate to meet the endpoint.
Basis for Conclusion:
Several acute oral lethality studies were available in a variety of species: rabbits, rats, and mice.
These studies were from the older (pre 1980) literature, did not report substance purity, and do
not fully conform to OPPTS or OECD guidelines, but given the magnitude of the LD50 values
the data are adequate for the evaluation of acute oral toxicity. Acute oral LD50 values generally
exceeded the current limit dose of 2,000 mg/kg. Reports that specified a 14-day observation
period are presented in detail.
Critical Studies:
Type: Acute oral toxicity
Species, strain, sex, number: Rabbit, Dutch-belted, 5 males/group
Doses: 0, 5,000, 7,500, and 10,000 mg/kg
Purity: Fyrol FR-2; purity not specifically reported
Vehicle: Not reported by Akzo-Nobel
Method: 14-Day post-dosing observation period; observations limited to mortality, clinical
signs, and necropsy. LD50 calculated according to Litchfield and Wilcoxon.
Results: Clinical signs shortly after dosing included ataxia, weakness, and diarrhea; survivors
normal by day 9. Necropsy revealed no abnormalities. Acute oral male rabbit LD50 = 6,800
mg/kg (95% CI 5,615-8,234 mg/kg).
Reference: Robust summary from Akzo-Nobel, 2001a, unpublished study conducted 1982
Type: Acute oral toxicity
3-4
Species, strain, sex, number: Rat, Sprague-Dawley, 5 males/group
Dose: 1,000, 2,150, 5,640, or 10,000 mg/kg
Purity: Fyrol FR-2; purity not specifically reported
Vehicle: None
Observation period: 14 days post dosing
Method: 14-Day post-dosing observation period; observations limited to mortality, clinical
signs, and necropsy; LD50 calculated according to Litchfield and Wilcoxon; not specified
whether fed or fasted at time of dosing.
Results: No effects at 1,000 mg/kg. Dose-related depression at or above 2,160 mg/kg; survivors
normal by day 5. No gross lesions in survivors; fatalities had congestion of heart, lung, and
liver. Acute rat oral LD50 = 3,160 mg/kg (95% CI 2,050-4,800 mg/kg)
Reference: Stauffer, 1972d; robust summary from Akzo-Nobel, 2001a
Type: Acute oral toxicity
Species, strain, sex, number: Mouse, Slc/ddY, 10/sex/dose
Purity: Not reported
Doses: For males: 0, 2,210, 2,380, 2,570, 2,780, 3,000, 3,240, and 3,500 mg/kg. For females: 0,
2,890, 2,040, 2,210, 2,380, 2,570, and 2,780 mg/kg.
Vehicle: Olive oil
Method: Observed for mortality and clinical signs for14 days. No body weight or gross
necropsy examination.
Results: Treated animals exhibited ataxic gait, hyperactivity, convulsion and death. No
mortality was observed in controls or in males at 2,210 mg/kg or females at 1,890 mg/kg. The
LD50 values were 2,670 mg/kg (2,520-2,830 mg/kg) for male mice and 2,250 (2,120-2,380
mg/kg) for female mice.
Reference: Kamata et al., 1989
Additional Studies and Information:
Other studies available only in secondary sources reported similar results. An oral LD50 of
>2,000 mg/kg was reported in male and female rats exposed to Tolgard TDCP MK1(Cuthbert,
1989a as reported in WHO, 1998); clinical signs observed during the first 5 days after dosing
included hypokinesia, piloerection, soiled coats, ataxia, chromodacryorrhea, rhinorrhea, and
salivation.
Acute Dermal Toxicity (OPPTS Harmonized Guideline 870.1200; OECD Guideline 402)
Conclusion:
The available acute dermal toxicity data were judged adequate to meet the endpoint.
3-5
Basis for Conclusion:
The available studies predate the preferred study guidelines, and did not report purity, but
together indicated no mortality at the guideline limit dose of 2,000 mg/kg. The report specifying
a 14-day observation period is presented in more detail.
Type: Acute dermal toxicity
Species, strain, sex, number: Rabbit, New Zealand albino, sex not specified, 4
Dose: 4,640 mg/kg
Purity: Fyrol FR-2; Stauffer, no data
Vehicle: None
Exposure period: 24 Hour
Method: 4 Rabbits tested occluded; 14-day observation period. Gross necropsy.
Results: Mortality after 14 days = 0/4. No overt signs of toxicity and no gross necropsy
findings. Therefore, dermal acute LD50 >4,640 mg/kg.
Reference: Stauffer, 1973a; additional information from robust summary in Akzo-Nobel, 2001a
Additional Studies and Information:
Other studies available only in secondary sources with minimal detail. A dermal LD50 of
>2,000 mg/kg was reported in male and female Sprague-Dawley rats exposed to Tolgard TDCP
MK1 (Cuthbert, 1989b as reported in WHO, 1998). No deaths and no clinical signs were noted
24 hours after treatment.
Acute Inhalation Toxicity (OPPTS Harmonized Guideline 870.1300; OECD Guideline 403)
Conclusion:
The available acute inhalation toxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
The available study on TDCPP predates the preferred guidelines. The duration was shorter than
currently recommended and no deaths were observed. Analysis of aerosol particle size,
however, was not mentioned so it is not known whether the size was respirable. Necropsies
were not performed.
Type: Acute inhalation toxicity
Species, strain, sex, number: Rat, Sprague-Dawley, 5 males and 5 females
Doses: 9.8 mg/L (9,800 mg/m3)
Purity: No data
Vehicle: None
Duration: 1 hour
Method: Observation period = 14 days. Observed daily for signs of toxicity and for mortality.
3-6
Results: No mortality after 14 days; initial signs of moderate depression
Reference: Stauffer,1973b
Additional Studies and Information:
Other studies available only in secondary sources reported similar results. An acute inhalation
LC50 of >5,220 mg/m3 was reported for Sprague-Dawley rats exposed to aerosol of TDCPP
(Amgard TDCP) (Anderson, 1990 as reported in WHO, 1998).
Acute Eye Irritation (OPPTS Harmonized Guideline 870.2400; OECD Guideline 405)
Conclusion:
The available eye irritation data were judged adequate to meet the endpoint.
Basis for Conclusion:
Two reasonably adequate studies report similar results in rabbits: mild reversible irritation of the
conjunctiva. The studies are summarized below.
Type: Acute eye irritation
Species, strain, sex, number: Rabbit, New Zealand White, sex not specified; 6
Doses: 0.1 mL
Purity: No data, Stauffer Fyrol FR-2
Vehicle: None
Method: Cited CFR [U.S. Federal Hazardous Substances Labelling Act] Section 191.12,
chapter 1, title 21. Following instillation of TDCPP, eyes were examined at 24, 48, and 72
hours.
Results: Mild conjunctival effects in 3/6 that cleared by 48 hours.
Reference: Stauffer, 1972c
Type: Acute (24-hour) eye irritation
Species, strain, sex, number: Rabbit, New Zealand White, male and female; 9 total
Doses: 0.1 mL
Purity: No data
Vehicle: None
Method: U.S. EPA Hazard Evaluation. 1978. Fed. Reg. 43: 163: pp. 37331-37402. Thirty
seconds following instillation of TDCPP, the treated eyes of three rabbits were washed, treated
eyes were not washed in 6 rabbits. The untreated eye of each animal served as a control. The
cornea, iris and conjunctiva of each eye were examined at 24, 48, and 72 hours, and at 4 and 7
days after instillation of TDCPP using the Draize scoring method.
Results: No signs of eye irritation were observed (average total Draize score of zero).
Reference: Stauffer, 1979; robust summary from Akzo-Nobel, 2001a for study dated 1979
3-7
Additional Studies and Information:
One hour following application of Tolgard TDCP MK1 to the eyes of New Zealand White
rabbits, slight conjunctival redness and slight discharge were noted (Cuthbert and Jackson, 1990
as reported in WHO, 1998); effects cleared by 24 hours.
Acute Dermal Irritation (OPPTS Harmonized Guideline 870.2500; OECD Guideline 404)
Conclusion:
The available dermal irritation data were judged adequate to meet the endpoint.
Basis for Conclusion:
Two reasonably adequate studies, patterned after guidelines in effect at the time, provide similar
results, indicating that TDCPP was a non-irritant when applied for 4 hours (consistent with
current guidelines) and a mild irritant when applied for 24 hours to rabbit skin. Additional
studies provide support. The studies are summarized below.
Critical Studies:
Type: Acute (24-hour) dermal irritation
Species, strain, sex, number: Rabbit, New Zealand, sex not specified, 6
Doses: 0.5 mL
Purity: Not reported; Stauffer Fyrol FR-2
Vehicle: None
Method: Cites "EPA protocol". Back hair was shaved, each rabbit tested on intact and abraded
skin, occlusive dressing removed after 24 hours, observations at 24 and 72 hours.
Results: No edema on intact or abraded skin in any of the 6 rabbits. Mild erythema was visible
at 24 hours but cleared by 72 hours, resulting in a score of 0.63. The report classified TDCPP as
a mild irritant.
Reference: Stauffer, 1979
Type: Acute (4-hour) dermal irritation
Species, strain, sex, number: Rabbit, not specified (but New Zealand white rabbits were used in
an eye irritation test conducted at the same time)
Doses: 0.5 mL
Purity: Not reported; Stauffer Fyrol FR-2
Vehicle: None
Method: Back hair shaved, each rabbit tested on intact and abraded skin, occlusive dressing
removed after 4 hours, observations at 4, 24 and 48 hours.
Results: No erythema or edema on intact or abraded skin in any of the 6 rabbits.
Reference: Stauffer, 1972c
3-8
Additional Studies:
Another study, on Tolgard TDCPP MK1, reported well-defined (score 2) erythema in 2 New
Zealand White rabbits and slight erythema in a third rabbit 1 hour after patch removal, but
duration of exposure was not specified (Cuthbert, 1989c as reported in WHO, 1998). Effects
cleared by 48 hours. The substance was classified as a skin irritant.
Skin Sensitization (OPPTS Harmonized Guideline 870.2600; OECD Guideline 429)
Conclusion:
The available skin sensitization data were judged adequate to meet the endpoint.
Basis for Conclusion:
A confidential study that reported negative results in a skin sensitization study in guinea pigs
was submitted that allows this endpoint to be adequately characterized.
A robust summary in a submission to the HPV Challenge program was located for an
unpublished industrial study stated to have been conducted under guideline. The summary
probably has not been reviewed by EPA, since this endpoint is not required for the HPV
program. Furthermore, the summary omits information necessary to determine study adequacy,
such as: the strain, sex, group size, substance purity, and dose levels. The summary claimed that
the doses were selected according to guideline, but the exact levels are not stipulated in the
guideline. Without the additional information, this study cannot be evaluated for adequacy.
Critical Studies:
Type: Dermal sensitization study
Species, strain, sex, number: Guinea pig, strain and sex not reported
Doses: Stated as according to guideline, but exact doses are not stipulated in guideline.
Purity: Not reported; Fyrol FR-2
Vehicle: Water
Method: Three pairs of intradermal injections into shaved shoulder: 1:1 Freunds Complete
Adjuvent (FCA) and saline, the test material, and 1:1 FCA and test material. Controls received
water in place of the test material. On day 6, 24 hours before topical induction application,
sodium lauryl sulfate was applied to sites to enhance local irritation. On day 7, test substance
was applied to sites (water for controls). On day 21, animals received challenge dose by dermal
application, occluded for 24 hours. Sites observed for irritation and sensitization (Grade 0-4).
Results: The sensitization score for Fyrol FR-2 was zero, indicating the substance is not a
chemical sensitizer.
Reference: Robust summary in Akzo-Nobel, 2001b for unpublished and unidentified study
dated 2001
3-9
SUBCHRONIC TOXICITY
Subchronic Oral Toxicity (28-day, 90-day, or combined with reproductive/developmental)
Conclusion:
The available subchronic oral toxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
A Japanese 90-day dietary study in mice (Kamata et al. 1989) provides limited relevant
information in the English abstract and data tables. The study was not adequate to characterize
this endpoint because histopathological analysis was apparently limited to the liver. A fertility
study by Wilczynski et al. (1983), discussed under the Reproductive Toxicity endpoint,
evaluated male rabbits exposed by oral gavage for 12 weeks, but did not involve treated females.
? Repeated Dose 28-Day Oral Toxicity in Rodents (OPPTS Harmonized Guideline
870.3050; OECD Guideline 407)
No study of this type was located.
90-Day Oral Toxicity in Rodents (OPPTS Harmonized Guideline 870.3100; OECD
Guideline 408)
Type: 90-Day repeated oral
Species, strain, sex, number: Mouse, Slc/ddY, 12/sex/dose
Doses: TDCPP at dietary concentrations of 0, 0.01, 0.04, 0.13, 0.42, and 1.33% in the diet,
resulting in reported average daily doses of 0, 13.2, 47.3, 171.0, 576.0, and 1,792.3 mg/kg/day in
males and 0, 15.3, 62.5, 213.6, 598.0, and 1,973.1 mg/kg/day in female mice
Purity: Not reported
Vehicle: None; added to diet
Exposure period, frequency: 90 days, ad lib
Method: Body weight, food consumption measured weekly. At 1 and 3 months in half the
animals, hematologic (erythrocyte, hemoglobin, hematocrit, and leukocyte counts) and clinical
chemistry parameters (total protein, albumin, albumin/globulin ratio, blood urea nitrogen,
glucose, total cholesterol, alkaline phosphatase, aspartate aminotransferase, alanine
aminotransferase). At 1 and 3 months, half the animals were necropsied and absolute and
relative organ weights were determined for brain, heart, lung, liver, kidney, and spleen. The
liver was examined for microscopic histopathology; the English text does not mention whether
other tissues were examined.
Results: At the highest dietary level, 1.33%, all mice exhibited emaciation, rough hair, and
tremor and died within 1 month. At 1.33%, food consumption was reduced and body weight loss
occurred in both sexes. Mean body weight gain was reduced by about 10% (estimated from
graph) in males at 0.42% throughout the study. The following statistically significant changes
3-10
occurred in treated groups compared to controls. Slight anemia (reduced hemoglobin; p<0.05) in
males at 0.42% after 3 months. Anemia (reduced hemoglobin at $0.13% after 1 month and at
0.42% at 3 months, erythrocyte and hematocrit at 0.42% at 1 and 3 months) in females (3-month
values p<0.01). Albumin/globulin ratios elevated in all treated male groups at 3 months.
Alkaline phosphatase elevated in females at 0.42% at 1 month but not later. Dose-related organ
weight elevations compared to controls observed at 3 months in males included relative liver
weight (+32-51%) at $0.13% and relative kidney weight (+39%) at 0.42%. Significant
elevations in organ weights in females at 3 months included relative liver weight (+16-51%) at
$0.04%, absolute (+30%) and relative (+34-40%) kidney weights at $0.13%, and absolute liver
weight (+40%) at 0.42%. The statistical significance of these organ weight elevations was
p<0.01 for rats exposed at $0.13% and p<0.05 for rats exposed at 0.04.%. Histopathology of the
liver (slight focal necrosis) was observed in only two females at 0.42%. The dietary level of
0.01% is a NOAEL of 15.3 mg/kg/day and the dietary level of 0.04% is a LOAEL of 62.5
mg/kg/day for liver and kidney weight elevations in female mice.
Reference: Kamata et al., 1989
? Combined Repeated Dose Toxicity Study with the Reproduction/Developmental
Toxicity Screening Test (OPPTS Harmonized Guideline 870.3650; OECD Guideline
422)
No studies of this type were located.
Subchronic Dermal Toxicity (21/28-day or 90-day)
Conclusion:
No available subchronic dermal toxicity data.
Basis for Conclusion:
No data exist for the subchronic dermal toxicity endpoint.
? 21/28-Day Dermal Toxicity (OPPTS Harmonized Guideline 870.3200 (OECD
Guideline 410)
? 90-Day Dermal Toxicity (OPPTS Harmonized Guideline 870.3250; OECD Guideline
411)
No studies of either type were located.
3-11
Subchronic Inhalation Toxicity (90-day)
Conclusion:
No available subchronic inhalation toxicity data.
Basis for Conclusion:
No repeated-exposure inhalation toxicity studies were located.
? 90-Day Inhalation Toxicity (OPPTS Harmonized Guideline 870.3465; OECD
Guideline 413)
No studies of this type were located.
REPRODUCTIVE TOXICITY
Conclusion:
The available reproductive toxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
A fertility assay in male rabbits exposed by oral gavage for 12 weeks prior to mating
(Wilczynski et al., 1983) partially characterizes this endpoint, but is not sufficient to satisfy the
reproductive toxicity endpoint since it was described only in an abstract and females were not
tested. Other studies (Hazleton, 1978; Tanaka et al., 1981) described below under
Developmental Toxicity reported that in pregnant female rats exposed orally to TDCPP, adverse
reproductive effects occurred only at maternally lethal doses. However, no study evaluated
reproductive function in females treated prior to mating.
The 2-year feeding bioassay in rats by Freudenthal and Henrich (2000; Bio/Dynamics, 1980,
1981), discussed below under Chronic Toxicity, provides reproductive histopathology data that
are, however, insufficient to satisfy the reproductive toxicity endpoint. This study provided
histopathology results for the testis, epididymis, seminal vesicle, ovary, and uterus for the
control and high-dose groups (0 and 80 mg/kg/day) after 1 year (10 scheduled
sacrifices/sex/group) and for survivors in all groups after 2 years; unscheduled sacrifices (rats
killed in a moribund state) were also examined. The 2-year exposure is too long to represent
reproductive toxicity, because of the confounding effects of aging; the results pointed to dose-
related effects in male reproductive organs (at $5 mg/kg/day, atrophy and decreased secretory
product of the seminal vesicles; at $20 mg/kg/day, testicular germinal atrophy with
oligospermia; and at 80 mg/kg/day, oligospermia and luminal accumulation of degenerated
seminal products in the epididymis). No significant effect was observed in females. The tested
doses, which were considerably lower than the guideline limit dose of 1,000 mg/kg/day, were not
3-12
high enough to induce significant reproductive histopathology after one year of exposure; 1/10
high-dose males had oligospermia. Thus, a LOAEL for reproductive effects following
subchronic (90-day) exposure is not available and cannot be extrapolated from the existing data,
but the chronic data indicate a LOAEL of 5 mg/kg/day for atrophy and decreased secretory
product of the seminal vesicles.
? Reproduction/Developmental Toxicity Screening (OPPTS Harmonized Guideline
870.3550; OECD Guideline 421)
? Combined Repeated Dose Toxicity Study with the Reproduction/Developmental
Toxicity Screening Test (OPPTS Harmonized Guideline 870.3650; OECD Guideline
422)
? Reproduction and Fertility Effects (OPPTS Harmonized Guideline 870.3800; OECD
Guideline 416)
No studies were available that met the specific designs of the three protocols listed above.
Additional Studies:
A study described in an abstract by Wilczynski et al. (1983) addresses fertility in male rabbits
exposed by oral gavage for 12 weeks prior to mating.
Type: Fertility
Species, strain, sex, number: Rabbit, strain not specified, 10 males/dose
Purity: Not reported
Doses: 0, 2, 20, or 200 mg/kg/day
Vehicle: Not reported
Exposure duration, frequency: 12 weeks, once by oral gavage daily
Method: Males treated for 12 weeks, then mated with untreated females. Body weight, clinical
signs, clinical chemistry, hematology, mating behavior, male fertility, sperm quantity and
quality, kidney and liver weights, gross and microscopic pathology (range of organs examined
not specified).
Results: High-dose animals had significantly increased absolute kidney weight and relative liver
weight. TDCPP had no effect on male reproductive parameters; there was no histopathology in
kidneys, liver, pituitaries, testes, or epididymides.
Reference: Wilczynski et al., 1983
DEVELOPMENTAL TOXICITY
Conclusion:
The available developmental toxicity data were judged adequate to meet the endpoint.
3-13
Basis for Conclusion:
Developmental toxicity studies in two strains of rats exposed to Fyrol FR-2 by oral gavage
followed methods consistent with OECD Guideline 414 (one study pre-dated the guideline).
Prenatal Developmental Toxicity Study (OPPTS Harmonized Guideline 870.3700; OECD
Guideline 414)
Type: Prenatal developmental toxicity
Species, strain, sex, number: Rat, Wistar, 15 pregnant females at the highest dose, 23-24
pregnant females in controls and other dose groups.
Purity: not reported
Doses: 0, 25, 50, 100, 200, and 400 mg/kg/day
Vehicle: Olive oil
Exposure duration, frequency: Once by oral gavage daily on gestational days (GD) 7-19.
Method: Body weight, food consumption, clinical signs, pregnancy rates, and necropsy of dams,
kidney weight; uterine contents (including implants and resorption) at day 20 of gestation,
corpora lutea; fetal viability, sex ratio and weight, crown-rump length, and external and skeletal
abnormalities.
Seven dams from each of the control and #200 mg/kg/day groups were permitted to litter
normally and evaluated for implantation sites, delivery index, number of live offspring at birth
and survival on PND 4, at 4th week, and at 10th week. Litters were culled to 10 offspring on
postnatal day 4 (PND 4) and subjected to behavioral tests (open field, water maze, rota rod,
inclined screen, pain reflex and Preyer's reflex). Absolute organ weights of 10 organs plus
testis, uterus and ovary were measured in offspring.
Results: Maternal mortality occurred only at 400 mg/kg/day: 11/15 died. Food consumption
was suppressed at 400 mg/kg/day and slightly at 200 mg/kg/day. At 400 mg/kg/day, mean body
weight loss occurred during GD 7-15, resulting in significantly (p<0.05) reduced terminal body
weight on GD20: ~17% lower than control group. Absolute and relative kidney weights were
significantly increased at 200 and 400 mg/kg/day. TDCPP at #200 mg/kg/day had no effect on
corpora lutea or mean numbers of implants, fetal body weight, fetal sex ratio, or the number of
dead or live fetuses. The numbers of dead fetuses and live fetuses were significantly (p<0.01)
changed compared to controls by the loss of one whole litter at 400 mg/kg/day. No increase in
malformations was observed in treated groups. For maternal toxicity, the NOAEL was 100
mg/kg/day and the LOAEL was 200 mg/kg/day for increased kidney weight. For fetal toxicity,
the NOAEL was 200 mg/kg/day and the LOAEL was 400 mg/kg/day for increased fetal death;
the highest dose of 400 mg/kg/day was a NOAEL for teratogenicity.
Postnatal observations: TDCPP at #200 mg/kg/day had no effect on implantation, delivery,
postnatal survival, behavior, functional test results, or absolute organ weights of offspring.
Reference: Tanaka et al., 1981
Type: Prenatal developmental toxicity
Species, strain, sex, number: Rat, Sprague-Dawley, 20 pregnant females/dose
Purity: not reported
3-14
Doses: 0, 25, 100, and 400 mg/kg/day
Vehicle: Corn oil
Exposure duration, frequency: Once by oral gavage daily on gestational days 6-15
Method: Body weight, food consumption, clinical signs, pregnancy rates, and necropsy of dams;
uterine contents (including implants and resorption) at day 19 of gestation, corpora lutea; fetal
viability and weight, crown-rump length, external, visceral (1/3 fetuses), and skeletal
abnormalities; extensive statistical analyses.
Results: High-dose dams exhibited clinical signs (urine stains, hunched appearance, and
alopecia); sporadic signs of urine stains and hunched appearance occurred in a few mid-dose
dams, but not at the low-dose. Food consumption was statistically lower in mid-dose dams on
days 7-11 and in high-dose group throughout (days 7-15). During Days 6-11, significant
(p<0.05) reductions in body weight gain in mid-dose dams and mean body weight loss at the
high dose; on days 11-15, only high-dose dams showed reduced body weight gain. Overall body
weights reduced in high-dose dams. TDCPP had no effect on implantation efficiency or mean
number of corpora lutea. Treatment at the high dose significantly (p<0.05) increased the number
of resorptions (to 14.4% compared to 6.7% in controls) and reduced fetal viability (to 85.6%
compared to 93.3% for controls). Decreased skeletal development in the high-dose groups is
related to growth retardation and decreased fetal size. The incidence of malformations was not
related to treatment. The study indicates a NOAEL of 25 mg/kg/day and a LOAEL of 100
mg/kg/day for maternal toxicity (clinical signs and transient reduction in body weight gain) and a
NOAEL of 100 mg/kg/day and a LOAEL of 400 mg/kg/day for developmental toxicity
(increased resorptions and fetal mortality).
Reference: Hazleton, 1978
? Combined Repeated Dose Toxicity Study with the Reproduction/Developmental
Toxicity Screening Test (OPPTS Harmonized Guideline 870.3650; OECD Guideline
422)
? Reproduction/Developmental Toxicity Screening (OPPTS Harmonized Guideline
870.3550; OECD Guideline 421)
No studies with the specific designs of the two tests listed above were available.
CHRONIC TOXICITY
Conclusion:
The available chronic toxicity data were judged adequate to meet the endpoint.
Basis for Conclusion:
The combined chronic toxicity/carcinogenicity assay in dietarily exposed rats is consistent with
the guideline (Freudenthal and Henrich, 2000; Bio/Dynamics, 1980).
3-15
? Chronic Toxicity (OPPTS Harmonized Guideline 870.4100; OECD Guideline 452)
No studies of this type were located.
Combined Chronic Toxicity/Carcinogenicity (OPPTS Harmonized Guideline 870.4300;
OECD Guideline 453)
The protocol of a 2-year feeding bioassay in rats was consistent with this guideline (Freudenthal
and Henrich, 2000; Bio/Dynamics, 1980). The published article focused on tumor results rather
than non-neoplastic effects.
Type: Combined oral chronic toxicity and carcinogenicity assay
Species, strain, sex, number: Rat, Sprague-Dawley, 60/sex/group
Purity: 95%
Doses: 0, 5, 20, and 80 mg/kg body weight/day
Vehicle: None other than feed
Route: In feed; diets blended weekly to achieve target doses
Exposure duration, frequency: 2 years, ad lib
Method: Examined twice daily for mortality and clinical signs, weekly physical examination.
Body weights and food consumption weekly for the first 13 weeks and biweekly thereafter.
Ophthalmoscopic examinations every 6 months. Extensive hematology, clinical chemistry and
urinalysis parameters at 3, 6, 12, 18, and 24 months. Ten/sex/dose randomly chosen for
termination at 12 months; the remainder at 24 months. Gross necropsy including organ weights
(8 organs plus gonads); histopathology of more than 30 tissues in control and high-dose rats; at
low- and mid-doses, histopathology limited to liver, kidneys, testes, and adrenals. Statistical
analyses.
Results: The following changes compared to controls were statistically significant (p<0.05).
Mortality increased in high-dose males (to 61.7% vs 43.3% for controls). Lower body weights
in high-dose males and females. Treatment had no effect on feed consumption. Signs of anemia
(lower hemoglobin, hematocrit, erythrocyte counts) in high-dose rats. At the mid-dose,
increased absolute and relative kidney weight males and females, absolute liver weight and
relative thyroid weight in males, and relative liver weight in females. At the high dose,
increased relative liver weight in males and absolute and relative thyroid weights in females.
Increases in the incidences of the following nonneoplastic lesions were statistically significant
(p<0.05) in treated groups compared to the control groups; changes were not strictly dose-related
in that incidences were depressed in high-dose groups. Kidney lesions (convoluted tubule
hyperplasia) in males at $20 mg/kg/day and in females at 80 mg/kg/day. Other systemic lesions
at 80 mg/kg/day involved the parathyroid (hyperplasia) in males and the liver (foci) and spleen
(erythroid/myeloid hyperplasia) in females. Reproductive system lesions in males involved
seminal vesicles (atrophy, decreased secretory product) at $5 mg/kg/day, testes (eosinophilic
material in lumen, periarteritis nodosa) at $20 mg/kg/day, and epididymis (oligospermia and
degenerated seminal product) at 80 mg/kg/day. (Tumor incidences are reported below under
Carcinogenicity.) The authors reported the lowest dose of 5 mg/kg/day as a NOAEL and the
3-16
mid-dose of 20 mg/kg/day as a LOAEL. However, as evaluated in NRC (2000), the lowest dose
of 5 mg/kg/day was a LOAEL for atrophy and decreased secretory product of the seminal
vesicle.
Reference: Freudenthal and Henrich, 2000; also Bio/Dynamics (1980), fiche 27 of 32 and
Bio/Dynamics (1981) fiche 6 of 6.
CARCINOGENICITY
Conclusion:
The available carcinogenicity data were judged adequate to meet the endpoint.
Basis for Conclusion:
Increased tumor incidences were observed in a combined chronic toxicity/carcinogenicity assay
in rats exposed to TDCPP in the diet (Freudenthal and Henrich, 2000).
? Carcinogenicity (OPPTS Harmonized Guideline 870.4200; OECD Guideline 451)
No studies of this type were located.
Combined Chronic Toxicity/Carcinogenicity (OPPTS Harmonized Guideline 870.4300;
OECD Guideline 453)
A 2-year feeding bioassay by Freudenthal and Henrich (2000) was consistent with this guideline.
Type: Combined oral chronic toxicity and carcinogenicity assay
Species, strain, sex, number: Rat, Sprague-Dawley, 60/sex/group
Purity: 95%
Doses: 0, 5, 20, and 80 mg/kg body weight/day
Vehicle: None other than feed
Route: In feed; diets blended weekly to achieve target doses
Exposure duration, frequency: 2, ad lib
Method: See description above under Chronic Toxicity
Results: The following neoplastic changes compared to controls were statistically significant
(p<0.05). Dose-related increased incidences at $20 mg/kg/day of renal cortical adenomas in
both sexes and testicular interstitial tumors in males, and at 80 mg/kg/day, of hepatocellular
adenomas and carcinomas combined in both sexes and adrenal cortical adenomas in females.
The NRC (2000) concluded that this study provides sufficient evidence of carcinogenicity of
TDCPP in rats following chronic oral exposure.
Reference: Freudenthal and Henrich, 2000; also Bio/Dynamics (1980, 1981)
3-17
NEUROTOXICITY
Conclusion:
The available neurotoxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
The delayed neurotoxicity component is satisfied by the existing data, but a developmental
toxicity study by Tanaka et al. (1981) that included postnatal behavioral examinations did not
fully satisfy the developmental neurotoxicity component. TDCPP gave negative results in single
acute and subchronic oral delayed neurotoxicity studies in hens and in limited postnatal testing
in rats exposed during gestation. A 2-year feeding bioassay in rats by Freudenthal and Henrich,
2000; Bio/Dynamics, 1980), discussed above under the Chronic Toxicity and Carcinogenicity
endpoints, reported no lesions of the cervical spinal cord, but a slight (not statistically
significant) increase in the incidence of gliomas of the brain in rats exposed to TDCPP at 80
mg/kg/day. The study authors could not determine whether this effect was related to exposure.
Delayed Neurotoxicity
Conclusion:
The available delayed neurotoxicity data were judged adequate to meet the endpoint.
Basis for Conclusion:
Several acute studies and one subchronic study for delayed neurotoxicity in the hen, summarized
below, give no evidence of acute cholinergic toxicity, inhibition of neurotoxic esterase (NTE)
activity, or delayed neurotoxicity for TDCPP. These studies, performed prior to the existence of
the guidelines, do not entirely conform to current guidelines, and may lack detail such as the
purity of the TDCPP sample. The lack of significant NTE inhibition following dosing with
10,000 mg/kg suggests that no additional testing for delayed neurotoxicity is needed for TDCPP.
? Acute and 28-Day Delayed Neurotoxicity of Organophosphorus Substances (OPPTS
Harmonized Guideline 870.6100; OECD Guideline 418, 419)
Unpublished industrial acute (1- or 5-day) and subchronic (90-day) delayed neurotoxicity assays,
which pre-date the guideline, are missing some details. One acute study employed a gavage dose
5 times higher than now specified under the guideline. The subchronic assay had a longer
duration and a larger group size than specified under the guideline.
3-18
Critical Studies
Type: Acute oral delayed neurotoxicity
Species, strain, sex, number: Hen, White Leghorn, 4/dose
Purity: Fyrol FR-2, purity not reported, clear colorless liquid
Doses: 420 mg/kg (highest dose specified in protocol)
Vehicle: test substance diluted 50% in corn oil
Positive control: 90 or 120 mg/kg/day tri-ortho-tylol phosphate (TOCP)
Route: Gavage
Exposure duration, frequency: Once daily on five consecutive days
Method: Navy MIL-H-19457B (SHIPS) protocol. Hens were weighed and graded on days 7, 9,
11, 14, 16, 18, 21, and 23 after the first dose for no signs, doubtful/minor signs, positive paralytic
signs, advanced paralytic signs, or death. Scores on the 21st day were compared with results for
TOCP. Necropsy not performed.
Results: No overt signs of neurotoxicity in with TDCPP treatment. Positive control caused
inability to walk, hypertension, ataxia, and prostration.
Reference: Bullock and Kamienski, 1972 as described in WHO, 1998; Stauffer 1972a
Type: Acute oral delayed neurotoxicity
Species, strain, sex, number: Hen, White Leghorn, 4/dose for TDCPP, 3/dose for controls
Purity: Fyrol FR-2, clear colorless liquid; one part of the report stated that the purity was not
reported, whereas another part of the report indicated purity >99%.
Doses: 10,000 mg/kg
Vehicle: None
Positive control: 500 mg/kg tri-ortho-cresyl phosphate (TOCP)
Negative control: 15 mg/kg tetraethyl pyrophosphate (TEPP)
Route: Oral gavage
Exposure duration, frequency: Once
Method: Twenty minutes before dosing, hens received atropine and 2-PAM to protect against
cholinergic effects. Hens were observed for toxic signs at 2-hour intervals for the first 8 hours.
Mortalities were recorded after 24 hours. Brains were harvested 24 hours after dosing and
analyzed for neurotoxic esterase (NTE) activity.
Results: Toxic signs were not reported specifically for TDCPP, but for all compounds tested at
the maximum tolerated dose, signs included listlessness and ataxia. Inhibition of NTE activity
was 7% for TDCPP and the negative control TEPP, but 85% for the positive control (TOCP).
The current guideline specifies that testing is not necessary at doses above 2,000 mg/kg.
Reference: Stauffer, 1978
Type: Subchronic oral delayed neurotoxicity
Species, strain, sex, number: Hen, adult, White Leghorn, 10/dose
Purity: Not reported
Doses: 0, 4, 20, and 100 mg/kg/day
Vehicle: Not reported
Route: Oral Gavage
3-19
Exposure duration, frequency: 90 days, daily
Method: Body weight. Daily observations for mortality and behavioral changes; evaluated for
signs of motor weakness 3 times per week. At termination, hens were necropsied and brain
(multiple sections), sciatic nerve, and spinal cord (cervical, thoracic and lumbar) were examined
histopathologically. TOCP was the positive control.
Results: Hens treated with TDCPP at the high dose exhibited mean reductions in body weight
during the latter part of the study, but no overt signs of neurotoxicity and no histopathological
effects in the nervous tissues. Conversely, the positive control hens exhibited consistently lower
body weight gain, clinical signs of toxicity (locomotor impairment and ataxia) that became more
severe with time. Histopathology results were not reported for the positive control.
Reference: Robust summary from Akzo-Nobel, 2001a; unpublished, unidentified study dated
1979
Neurotoxicity (Adult)
Conclusion:
The available adult neurotoxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
The chronic oral bioassay by Freudenthal and Henrich (2000; Bio/Dynamics,1980, 1981)
reported no lesions of the brain or spinal cord in rats exposed to TDCPP at doses as high as 80
mg/kg/day for 2 years, but no functional tests of neurotoxicity were performed.
? Neurotoxicity Screening Battery (OPPTS Harmonized Guideline 870.6200; OECD
Guideline 424)
No studies of this type were located.
Developmental Neurotoxicity: Developmental Neurotoxicity Study (OPPTS Harmonized
Guideline 870.6300)
Conclusion:
The available developmental neurotoxicity data were judged inadequate to meet the endpoint,
although the available tests suggest that TDCPP is not a developmental neurotoxin.
Basis for Conclusion:
No studies of this specific design were located. A Japanese-language gavage study by Tanaka et
al. (1981), described above under Developmental Toxicity, included postnatal neurobehavioral
tests (open field, water maze, rota rod, inclined screen, pain reflex, and Preyer's reflex) of
sensory and motor function in rats. Full descriptions of these tests were not available in the
3-20
English summary and therefore could not be compared to the guideline protocol. The study
reported no adverse effect in these tests for offspring of dams that were exposed on gestational
days 7-15 at doses as high as 200 mg/kg/day (the highest tested non-lethal dose that was a
LOAEL for increased kidney weight). This study does not fully satisfy the developmental
neurotoxicity endpoint because it omitted some parameters specified under the guideline:
developmental landmarks for sexual maturity, auditory startle test, and neurohistopathological
examinations.
Additional neurotoxicity studies:
? Schedule-Controlled Operant Behavior (mouse or rat)
? OPPTS Harmonized Guideline 870.6500
? Peripheral Nerve Function (rodent)
? OPPTS Harmonized Guideline 870.6850
? Sensory Evoked Potentials (rat, pigmented strain preferred)
? OPPTS Harmonized Guideline 870.6855
These studies may be indicated, for example, to follow up neurotoxic signs seen in other studies,
or because of structural similarity of the substance to neurotoxicants that affect these endpoints.
These studies may be combined with other toxicity studies.
Conclusion: These endpoints do not appear to be applicable to TDCPP.
Basis for Conclusion: Although there are no studies addressing these endpoints, there are no
reliable data for TDCPP, and no structure-activity considerations, that indicate a need for these
follow-up studies.
Other Neurotoxicity Data
Cholinesterase inhibition
Fyrol FR-2 administered at 0, 2,000, or 3,980 mg/kg in corn oil was administered to groups of 10
male Sprague-Dawley rats by oral gavage had no effect on plasma or erythrocyte cholinesterase
levels measured 4 or 14 hours after dosing (Stauffer, 1972b).
IMMUNOTOXICITY
Conclusion:
The available immunotoxicity data were judged inadequate to meet the endpoint.
3-21
Basis for Conclusion:
The only study evaluating the potential immunotoxicity of TDCPP (Luster et al., 1981) predates
the guideline for immunotoxicity (note that the OPPTS guideline cites other works by this
author). There is some uncertainty as the test material, reported as Fyrol FR2, but mis-identified
by the authors as tris(2,3-dichloropropyl) phosphate. The study methods differed from the
guideline in the short exposure period (4 rather than 28 days), parenteral administration (rather
than oral or inhalation route), measurement of serum immunoglobulins in non-immunized rather
than immunized mice, and the omission of some tests (enumeration of immunological cell
subpopulations, test for NK-cell activity). The results do not provide dose璻esponse information
as to immunotoxicity of TDCPP following subchronic exposure by oral or inhalation routes of
exposure.
Immunotoxicity (OPPTS Harmonized Guideline 870.7800)
Critical study
Type: Immunotoxicity, subcutaneous, acute
Species, strain, sex, number: Mouse, B6C3F1, 6-8 females/dose
Doses: 0, 0.25, 2.5, or 25 mg/kg/day (Total cumulative doses of 0, 1, 10, or 100 mg/kg)
Identity: Stauffer Fyrol FR-2, lot 4670-3-23. This is the same lot as TDCPP tested in the 2-year
oral assay by Freudenthal and Henrich (2000)
Purity: Stauffer, purity >95%
Vehicle: Corn oil
Route: Subcutaneous injection
Exposure duration, frequency: 4 days, once daily
Method: Observations included body weight, hematology, clinical chemistry (5 parameters)
terminal necropsy, organ weights (liver, spleen and thymus), histopathology of spleen, thymus,
and eight other organs, plaque-forming assay response to sheep red blood cells, and serum
immunoglobulin quantification (non-immunized mice only). Non-guideline tests included
proliferative capacity of granulocyte-macrophage progenitor cells (bone marrow), in vitro
lymphoproliferative (LP) responses to mitogens, delayed hypersensitivity response to keyhole
limpet hemocyanin. Extensive statistical analysis.
Results: Twenty percent of high-dose mice exhibited lymphoid depletion of the thymus.
Statistically significant decreases in vitro lipopolysaccharide (B-cell antigen) at 2.5 mg/kg/day
and concanavalin A (T-cell antigen) at 25 mg/kg/day.
Reference: Luster et al., 1981
GENOTOXICITY
Conclusion: The available genotoxicity data were judged adequate to meet the endpoint.
3-22
Basis for Conclusion:
TDCPP has been tested in in vitro and in vivo genotoxicity assays conducted in prokaryotic and
eukaryotic cells under methods similar to guidelines. Results of in vivo tests (mutation in
Drosophila, chromosomal aberration in mice) were negative, but positive results were reported
in several in vitro assays (mutagenicity in bacterial and mammalian cells, chromosomal
aberration).
Gene Mutation in Vitro:
C Bacterial Reverse Mutation test (OPPTS Harmonized Guideline 870.5100; OECD
Guideline 471)
Type: Bacterial reverse mutation
Species, strain: Salmonella typhimurium TA97, TA98, TA100, TA1535, TA1537
Metabolic activation: Tested with and without S9 from livers of Aroclor-induced male
Sprague-Dawley rats or male Hamsters
Concentrations: 0, five concentrations between 10 and 10,000 :g/plate.
Purity: 94.4%
Method: Preincubation (20 minutes) and plate incorporation (48 hours) at 37癈. Positive
controls were used; DMSO was the solvent. Triplicate plates per concentration. All assays
repeated within 1 week.
Results: In three different laboratories, TDCPP tested positive in strains TA97 and TA100 in the
presence of S9 from Aroclor-induced hamster liver and in strain TA1535 in the presence of S9
from Aroclor-induced rat or hamster liver. Positive controls gave expected increases. Solvent
control and all other test combinations were negative.
Reference: Mortelmans et al., 1986
Type: Bacterial reverse mutation
Species, strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation: Tested with and without Kanechlor 500 (PCB)-induced liver S9 from
male Wistar rats
Concentrations: 0, 10, 30, 100, and 300 :g/plate.
Purity: Assayed as ~94% TDCPP, plus ~6% bis(1-chloromethyl-2-chloroethyl)(2,3
dichloropropyl) phosphate.
Method: Plate incorporation, 48-hour incubation at 37癈. Cited Ames protocol, which
presumes the use of replicates and positive controls.
Results: No increase in revertants in any strain without activation or in strains TA98, TA1537,
or TA1538 with activation. Weak increases in TA100 and TA1535 at the highest concentrations
with S9.
Reference: Nakamura et al., 1979
3-23
Additional Studies
Other S. typhimurium assays in which S9 was prepared from phenobarbital-induced rat liver
reported mutagenicity of TDCPP in strain TA98 by liquid preincubation assay (Abe and Urano,
1994) and in TA100 by plate incorporation assay (Gold et al., 1978; Soederlund et al., 1985).
Majeska and Matheson (1983) reported dose-related positive results for TDCPP and its
metabolite 1,3-dichloro-2-propanol in TA100 with S9 (phenobarbital-induced) in standard plate
assays at concentrations up to 500 :g/plate. In a liquid preincubation quantitative assay, results
for TDCPP were essentially negative--only increasing mutation frequencies at cytotoxic
concentrations (survival <3%). However, its metabolites increased mutant frequencies with less
cytotoxicity: 1,3-dichloro-2-propanone positive at <80% survival and 1,3-dichloro-2-propanol
positive at <30% survival.
TDCPP was not mutagenic in S. typhimurium strains TA100, TA1535, or TA1538 without
activation or when Aroclor-induction was used to prepare the S9 fraction (Prival et al., 1977);
the highest exposure level was 10 :L per plate.
C In vitro Mammalian Cell Gene Mutation Test (OPPTS Harmonized Guideline
870.5300; OECD Guideline 476)
Type: Mammalian Cell Gene Mutation Test: Forward Mutation
Species, strain: Mouse lymphoma L5178Y
Metabolic activation: Tested with and without phenobarbital-induced liver S9 from male mice
Concentrations: 0, and five concentrations up to ~32 nL/mL without S9, and six concentrations
up to 70 nL/mL with S9. Test conditions chosen based on preliminary assays so that 50%
growth reduction occurred at highest concentration.
Purity: Not reported
Method: Selection of forward mutation from TK+/- to TK-/- genotype. Activity compared to
tris(2,3-dibromopropyl)phosphate (TBPP).
Results: TDCPP yielded negative results with or without activation. TBPP was negative
without, but positive with activation.
Reference: Brusick et al., 1979; also Litton Bionetics, Inc., 1977
Type: Mammalian Cell Gene Mutation Test: Forward Mutation
Species, strain: V79 Chinese hamster lung cells
Metabolic activation: Tested with phenobarbital-induced liver S9 from male rats
Concentrations: 0, 0.02 mM TDCPP. Test conditions chosen based on preliminary assays.
Purity: Not reported
Method: In two experiments, selection of 6-thioguanine-resistant colonies. Activity compared
to tris(2,3-dibromopropyl)phosphate (TBPP).
Results: TDCPP with S9 did not increase mutation frequency. TBPP yielded positive results.
Reference: Soederlund et al., 1985
3-24
Gene Mutation in Vivo:
C Sex-linked Recessive Lethal test in Drosophila melanogaster (OPPTS Harmonized
Guideline 870.5275)
Type: Sex-linked Recessive Lethal test
Species, strain: Drosophila melanogaster, 100 males/concentration
Metabolic activation: None
Concentrations: 2.5 and 25% in feed (1% gum tragacanth in 3% sucrose)
Purity: Technical-grade Fyrol FR-2, purity not reported
Method: TDCPP added to feed of males for 24 hours, subsequently mated with virgin
unexposed females
Results: No evidence of toxicity or increase in the percentage of sex-linked recessive lethal
mutations.
Reference: Brusick and Jagannath, 1977 as described in WHO, 1998; also Litton Bionetics, Inc.,
1976
Chromosomal Aberration in Vitro:
C In Vitro Mammalian Chromosome Aberration Test (OPPTS Harmonized Guideline
870.5375)
Type: In vitro chromosome aberration assay
Species, strain: Mouse lymphoma L5178Y
Metabolic activation: None, phenobarbital-induced or PCB-induced
Concentrations: 0, 0.01 to 0.1 :L/mL for non-induced, phenobarbital-induced or PCB-induced
mouse
Purity: Not reported
Method: 4-hour exposure to TDCPP with or without activation. Chromosomal aberrations
scored in 50 metaphase spreads per concentration.
Results: TDCPP caused increases chromosomal aberrations (up to 40%) with PCB- or
phenobarbital-induction compared to noninduced S9.
Reference: Brusick et al., 1979; also Litton Bionetics, Inc., 1977
Additional Information
One confidential study reported negative results for TDCPP in cultured Chinese hamster ovary
cells with or without metabolic activation. Another confidential study reported positive results
in human lymphocytes with metabolic activation.
C In vitro Sister Chromatid Exchange Assay (OPPTS Harmonized Guideline
870.5900)
Type: In vitro sister chromatid exchange assay
3-25
Species, strain: Mouse lymphoma L5178Y
Metabolic activation: None, phenobarbital-induced or PCB-induced
Concentrations: 0, 0.005-0.03 :L/mL for phenobarbital-induced (4 concentrations), and 6
concentrations up to 0.070 :L/mL for non-induced or PCB-induced mouse
Purity: Not reported
Method: Ten cells per concentration were analyzed.
Results: TDCPP increased the incidence of sister chromatid exchanges in mouse lymphocytes
under all three test conditions.
Reference: Brusick et al., 1979; also Litton Bionetics, Inc., 1977
Additional Information
One submitted confidential study reported negative results in a sister chromatid exchange assay.
The data for this study are not adequate because the cell line was not identified. Fyrol FR-2 did
not induce sister chromatid exchanges when applied to 3- to 4-day-old chicken embryos (Bloom,
1984).
Chromosomal Aberration in Vivo:
C Mammalian Bone Marrow Chromosomal Aberration Test (OPPTS Harmonized
Guideline 870.5385)
The available study provides sufficient evidence that TDCPP did not induce chromosomal
aberrations in mice exposed at the maximum tolerated dose of 760 mg/kg.
Type: Bone marrow chromosomal aberration in vivo
Species, strain: Mouse, CD-1, 4-8 males/group
Metabolic activation: None
Concentrations: 0, 0.05, 0.17, and 0.5 mL/kg; using the specific gravity of 1.52, the doses were
0, 76, 260, or 760 mg/kg. The highest dose was the maximum tolerated dose. Negative control
was DMSO
Exposure duration, frequency: By oral gavage in once or daily on 5 consecutive days.
Purity: Technical grade; Not reported
Method: Mice were sacrificed at 6, 24, and 48 hours after single dose or 6 hours after the last of
5 doses. Between 233 and 400 cells were scored, rather than 500/animal. Triethylenemelamine
was positive control.
Results: No evidence of increased frequency of chromosomal aberrations with TDCPP. TBPP
was also negative at doses up to 1,000 mg/kg. Positive control produce expected large increase
in micronucleated polychromatic erythrocytes.
Reference: Brusick et al., 1979; Litton Bionetics, Inc., 1978
C Mammalian erythrocyte micronucleus test (OPPTS Harmonized Guideline
870.5395)
3-26
TDCPP administered as 2,000 mg/kg by an unspecified route to mice did not induce micronuclei
in bone marrow erythrocytes (Thomas and Collier, 1985 as reported in WHO, 1998).
DNA Damage and Repair
C Unscheduled DNA synthesis in mammalian cells in culture (OPPTS Harmonized
Guideline 870.5550)
Type: Unscheduled DNA synthesis in mammalian cells (hepatocytes) in culture
Species, strain: Rat, Wistar, male
Metabolic activation: With or without phenobarbital-induction
Concentrations: 0, 0.05, and 0.1 mM
Purity: Not reported
Vehicle: DMSO
Method: Cultured hepatocytes exposed to TDCPP or TBPP for 18-19 hours. Incorporation of
radiothymidine into DNA.
Results: TDCPP was not genotoxic at 0.05 mM, but at 0.1 mM, a moderate response was
observed in hepatocytes from untreated rats, but not phenobarbital-treated rats. TBPP, the
positive control, yielded positive results in induced and non-induced hepatocytes.
Reference: Soederlund et al., 1985
Additional Information
A confidential study reported negative results for TDCPP and its metabolites (not identified) in
cultured primary hepatocytes from male Sprague-Dawley rats.
3-27
Ecotoxicity
Aquatic Organism Toxicity
Acute Toxicity to Freshwater and Marine Fish (OPPTS Harmonized Guideline 850.1075;
OECD Guideline 203)
Conclusion:
The available acute toxicity data for freshwater fish (cold- and warm-water species) and
saltwater fish were judged inadequate to meet the endpoint. The available acute fish toxicity
studies are summarized in Table 3-1. However, if the results of the SafePharm study (1993a),
cited by IPCS (1998) (see below), are confirmed independently, the acute toxicity data for cold
freshwater fish species might meet the endpoint given the high degree of agreement of the two
available studies in rainbow trout.
Basis for Conclusion:
Freshwater Fish
Ahrens et al. (1979) tested the toxicity to goldfish (Carassius auratus) of tris (1,3-dichloro-2
propyl) phosphate (TDCPP) released from fabric treated with the flame retardant. Laundered or
unlaundered sections of garment that had been treated with Fyrol FR-2, were placed in tanks
with six goldfish. Fish in the tank with the unlaundered section became sluggish and all died
within 3 hours. The concentration of Fyrol FR-2 in the test water reached 30 mg/L. Fish
exposed for 96 hours to the laundered section of garment did not exhibit signs of toxicity. In
another study, TDCPP in water at 1 mg/L was not toxic to goldfish after 168 hours, but 5 mg/L
of TDCPP killed all (6/6) goldfish within 24 hours (Eldefrawi et al., 1977). The studies by
Ahrens et al. (1979) and Eldefrawi et al. (1977) did not evaluate toxicity using a range of
concentrations of TDCPP in water and, thus, cannot be used to derive an LC50.
Sasaki et al. (1981) estimated that the 96-hour LC50 values for killifish (Oryzias latipes) and
goldfish were 3.6 mg/L and 5.1 mg/L, respectively. It appears that mortality was not evaluated
in a control group of fish. It is unclear if the TDCPP concentrations in water reported by Sasaki
et al. (1981) are measured or nominal values. The latter point is important because a parallel
study indicated that the amount of TDCPP added to test water declines rapidly and less than 40%
of the original amount of TDCPP remains in the test water after 96 hours (Sasaki et al., 1981).
Thus, the lethal concentrations of TDCPP could be lower than the reported LC50 values.
Sasaki et al. (1981) reported deformation of the spine in 7/10 killifish exposed to 3.5 mg/L
TDCPP for 24 hours. However, Sasaki et al. (1981) do not provide sufficient information
regarding the spine deformation in killifish to make meaningful use of these observations. It is
unclear whether the deformations were observed in the acute toxicity study or in a separate assay
using killifish only. It appears that deformation was tested at only one concentration and a
control group of fish was not evaluated.
3-28
Another study showed that the 96-hour LC50 of TDCPP in rainbow trout (currently classified as
Oncorhynchus mykiss) was 1.4 mg/L (95% CI: 0.9-1.9 mg/L) (Unpublished study conducted in
1990, summarized in Akzo-Nobel, Inc., 2001a,b). A NOEC was not observed since one fish
died at 0.63 mg/L, the lowest concentration tested. Compound purity was not provided in the
summary and the reported concentrations of TDCPP in the test water appear to be nominal
values. The guideline for acute toxicity in fish (OPPTS 850.1075) indicates that test
concentrations must be measured during the test if, as was the case in this study, aeration is used.
Thus, the study reported by Akzo-Nobel, Inc. (2001a,b) does not meet the criteria established by
the guideline. The studies by Sasaki et al. (1981) and Akzo-Nobel, Inc. (2001a,b) suggest that
the 96-hour LC50 for TDCPP in fish is in the range of 1 to 5 mg/L, making it moderately toxic to
fish. However, the data are inadequate to satisfy the acute toxicity endpoint for freshwater fish.
A 96-hour LC50 of 1.1 mg/L and a NOEC of 0.56 mg/L for TDCPP in rainbow trout
(SafePharm, 1993a) were reported in IPCS (1998). Although the results of the study by
SafePharm (1993a) are in agreement with those of Akzo-Nobel, Inc. (2001a,b), the study by
SafePharm (1993a), or a study summary, was not available to allow for an independent
evaluation of these data. Confirmation of the results of the study by SafePharm (1993a) might
allow the acute toxicity endpoint for freshwater fish to be satisfied.
Marine Fish
No acute toxicity studies in saltwater fish species were located.
3-29
Table 3-1. Summary of available acute fish toxicity studies for tris(1,3-dichloro-2-propyl)phosphate [TDCPP] (CASRN: 13674-87-8)a
Selected Study Design Parametersb
No. of
Study Species 96-Hour Study Concentrations Fish/ Analytical
Reference Tested LC50 Type Tested Conc Monitoring Water Chemistry Solvent Comments on the Data
Ahrens et Goldfish None Static None 6 Yes. The pH: NR None A laundered or
al., 1979 (Carassius concentration Temp: 20癈 unlaundered 38 cm x 64
auratus) of Fyrol FR-2 DO: NR cm section of garment
in water was Hardness: NR (0.24 square meter area;
227 g/m3), which had been
determined Water volume: 20 L
by gas Electrical treated with Fyrol FR-2,
chromatograp conductivity: 290 was placed in tanks with
hy. micromhos/cm six goldfish.
Fish in the tank became
progressively more
sluggish and all died within
3 hours. The measured
concentration of Fyrol FR
2 in the test water was 30
mg/L.
Fish exposed for 96 hours
to the same section of
fabric after it had been
laundered did not die.
Data for mortality in
control fish were not
presented in the study.
Goldfish are not a
designated test species, as
per OPPTS 850.1075 (Fish
Acute Toxicity Test,
Freshwater and Marine).
The study cannot be used
3-30
Table 3-1. Summary of available acute fish toxicity studies for tris(1,3-dichloro-2-propyl)phosphate [TDCPP] (CASRN: 13674-87-8)a
Selected Study Design Parametersb
No. of
Study Species 96-Hour Study Concentrations Fish/ Analytical
Reference Tested LC50 Type Tested Conc Monitoring Water Chemistry Solvent Comments on the Data
Akzo- Rainbow 1.4 mg/L Static Controls, 0.63, 10 No pH: 7.14-7.78 None reported All mortalities occurred
Nobel, trout 1.25, 2.5, 5, 10 Temp: 11.8-14.8 癈. within the first 24 hours.
Inc., (Salmo (95% CI: mg/L DO: 92-100% of air Mortality was dose related.
2001a,b gairdneri) 0.9-1.9 saturation value One fish died in the lowest
(Study mg/L) Hardness: 218-228 dose group (0.63 mg/L).
conducted mg/L as CaCO3.
in 1990) All fish died in the 5 and
10 mg/L groups.
A NOEC was not observed.
3-31
Table 3-1. Summary of available acute fish toxicity studies for tris(1,3-dichloro-2-propyl)phosphate [TDCPP] (CASRN: 13674-87-8)a
Selected Study Design Parametersb
No. of
Study Species 96-Hour Study Concentrations Fish/ Analytical
Reference Tested LC50 Type Tested Conc Monitoring Water Chemistry Solvent Comments on the Data
Eldefrawi Goldfish None Static 1 and 5 mg/L in 6 None pH: NR Water or Fish were exposed to 1 or 5
et al., 1977 (Carassius water reported Temp: 20癈 acetone mg/L TDCPP in water or
auratus) DO: NR acetone. None of the fish
Hardness: NR in the 1 mg/L treatment
Electrical had died after 168 hours.
conductivity: 290
micromhos/cm All fish in the 5 mg/L
treatment died within 24
hours.
The most conspicuous
signs of toxicity were
sluggishness and
disoriented swimming prior
to death.
Mortality in control fish
was not reported.
Goldfish are not a
designated test species, as
per OPPTS 850.1075 (Fish
Acute Toxicity Test,
Freshwater and Marine).
The study cannot be used
to establish an LC50 value.
3-32
Table 3-1. Summary of available acute fish toxicity studies for tris(1,3-dichloro-2-propyl)phosphate [TDCPP] (CASRN: 13674-87-8)a
Selected Study Design Parametersb
No. of
Study Species 96-Hour Study Concentrations Fish/ Analytical
Reference Tested LC50 Type Tested Conc Monitoring Water Chemistry Solvent Comments on the Data
Sasaki et Killifish Killifish: Static NR 7 to 9 Unclear if pH: NR NR Fish were acclimated at
al., 1981 (Oryzias 3.6 mg/L conducted Temp: 25癈. least for 10 days at 25 癈.
latipes) DO: NR
Hardness: NR The test concentrations
Electrical used were not reported. A
conductivity: NR control group was not
tested.
Killifish, but not goldfish,
are a designated test
Goldfish Goldfish: species, as per OPPTS
(Carassius 5.1 mg/L 850.1075 (Fish Acute
auratus) Toxicity Test, Freshwater
and Marine).
Deformation of the spine
was observed in 7/10
killifish exposed to 3.5
mg/L TDCPP for 24 hours.
a
Studies that were either published in a foreign language or that were not readily and that were not critical to the hazard assessment were not retrieved.
b
NR: Not reported
3-33
Acute Toxicity to Freshwater Invertebrates (OPPTS Harmonized Guideline 850.1010;
OECD 202)
Conclusion:
The available acute toxicity data for freshwater invertebrates were judged inadequate to meet the
endpoint. However, if the results of the study cited by IPCS (1998) (see below) are confirmed
independently, the data might meet the endpoint given the high degree of agreement of the two
available studies in freshwater invertebrates.
Basis for Conclusion:
The available data are summarized in Table 3-2. A flow-through study revealed a 48-hour LC50
of TDCPP with Daphnia magna of 3.8 mg/L (95% CI: 3.5-4.2 mg/L) and a NOEC of 1.6 mg/L
(Unpublished study conducted in 1999, summarized in Akzo-Nobel, Inc., 2001a,b). Although
some of the conditions of the study design (such as number of organisms, and water temperature
and chemistry) appear to meet OPPTS Harmonized Guideline 850.1010, other aspects of the
study, including compound purity and condition and fertility of the organisms in culture, were
not reported in the summary. The amount of solvent used in the control group and the TDCPP
treatments might have exceeded the recommended maximum solvent concentration, as per the
OPPTS Guideline (100 mg/L), but this does not appear to have affected the study results. A 48
hour LC50 of 4.6 mg/L and a NOEC of 1.8 mg/L were reported for daphnia in a study by
SafePharm (1993b), as cited in IPCS (1998). Although the results of the study by SafePharm
(1993b) are in agreement with those of Akzo-Nobel, Inc. (2001a,b), the study by SafePharm
(1993b), or a study summary, was not available to allow for an independent evaluation of these
data. Confirmation of the results of the study by SafePharm (1993b) might allow the acute
freshwater invertebrate toxicity endpoint to be satisfied.
Acute Toxicity to Marine/Estuarine Invertebrates (OPPTS Harmonized Guideline
850.1035)
Conclusion:
No available acute marine/estuarine invertebrate toxicity data.
Basis for Conclusion:
No acute toxicity studies in marine/estuarine invertebrate species were located.
3-34
Table 3-2. Summary of available acute invertebrate toxicity studies for tris(1,3-dichloro-2-propyl)phosphate [TDCPP] (CASRN: 13674-87-8)a
Selected Study Design Parameters
No. of
Study Species 48-Hour Study Concentrations Organisms/ Analytical Water
Reference Tested LC50 Type Tested Concentration Monitoring Chemistry Solvent Comments on the Data
Akzo- Daphnia 3.8 Flow- Negative control, 10 Yes pH: 8.3 Dimethyl Daphnids in the negative and
Nobel, Inc., magna mg/L through solvent control Temp: formamide solvent control groups appeared
2001a,b (95% (dimethyl 20?癈 normal, as did the organisms in
DO: $8.5
(Study CI: 3.5 formamide), 0.98, the 0.98 and 1.6 mg/L groups.
conducted in 4.2 1.6, 2.8, 3.8, 5.1 mg/L (94% Mortality in the 2.8, 3.8, and 5.1
1999) mg/L) mg/L of air mg/L groups was 0, 70, and
saturation 80%, respectively. Daphnids
value) (15%) in the 2.8 mg/L group
Hardness: were lethargic at study
126 mg/L as termination.
CaCO3.
The amount of solvent used in
the control group and the
TDCPP treatments is estimated
to be approximately 300 mg/L.
This exceeds the recommended
maximum solvent concentration
of 100 mg/L. The estimate is
based on a reported
dimethylformamide volume of
0.1 ml, a test chamber volume
of 300 ml and a specific gravity
of 0.95.
a
Studies that were either published in a foreign language or that were not readily and that were not critical to the hazard assessment were not retrieved.
3-35
Chronic Toxicity to Freshwater and Marine Fish (OPPTS Harmonized Guideline
850.1400; OECD Guideline 210)
Conclusion:
No available chronic toxicity data for freshwater and marine fish.
Basis for Conclusion:
No chronic toxicity studies in freshwater and marine fish were located.
Chronic Toxicity to Freshwater Invertebrates (OPPTS Harmonized Guideline 850.1300;
OECD 211) and Chronic Toxicity to Marine/Estuarine Invertebrates (OPPTS Harmonized
Guideline 850.1350)
Conclusion:
No available chronic toxicity data for freshwater and marine/estuarine invertebrates.
Basis for Conclusion:
No chronic toxicity studies in freshwater and marine/estuarine invertebrates were located.
Algal Toxicity (OPPTS Harmonized Guideline 850.5400; OECD Guideline 201)
Conclusion:
The available algal toxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
The available data are summarized in Table 3-3. The summary of a 96-hour algal toxicity study
(Unpublished study conducted in 1992, summarized in Akzo-Nobel, Inc., 2001a,b) indicates that
the study does not meet the OPPTS Harmonized Guideline 850.5400. The pH and temperature
of the test water during the study were outside of the acceptable ranges for Selenastrum
capricornutum, as per Guideline 850.5400. Moreover, the two highest concentrations tested
exceed the estimated water solubility of TDCPP (42 mg/L) and the concentrations tested were
apparently not verified analytically. Additional information, including test substance purity,
hardness, DO, TOC, TSS, exposure vessel size and head space, and measured chemical
concentrations, were not provided in the summary. Also, there is no evidence that positive
controls were used in order to establish that the algae were responding in the expected manner to
a known chemical. The deviations from the OPPTS Guideline indicate that the study is
inadequate to satisfy the algal toxicity endpoint. Another study indicates that TDCPP at 10 mg/L
had no effect on growth or biomass of the algal species Scenedesmus subspicatus exposed for 72
3-36
hours (Unpublished study conducted by SafePharm, 1994, cited in IPCS, 1998). The study, or a
study summary, was not available for the study by SafePharm (1994) to allow for an independent
evaluation of these data.
3-37
Table 3-3. Summary of available algal toxicity studies for tris(1,3-dichloro-2-propyl)phosphate [TDCPP] (CASRN: 13674-87-8)a
Selected Study Design Parametersb
Study Species EC50, NOAEC, Study Concentration Analytical Water Comments on the
Reference Tested and LOAEC Type Range Tested Monitoring Chemistry Solvent Data
Akzo- Selenastrum 96-hour EbC50 Static 0 (negative No Temp: 21癈 None A number of problems
Nobel, Inc., capricornutum (biomass) control), 2, 6, 18, pH: 6.7-7.9 reported are evident with this
2001a,b = 12 mg/L (95% 54, or 162 mg/L DO: NR study, namely the pH
(Study CI: 10-15 mg/L). Hardness: NR changed markedly
conducted in during the study, and the
1992) 96-hour ErC50 reported pH and water
(growth rate) = 39 temperature were outside
mg/L (95% CI: of the recommended
31-50 mg/L). values for this algal
species.
96-hour NOAEC:
6 mg/L.
a
Studies that were either published in a foreign language or that were not readily and that were not critical to the hazard assessment were not retrieved.
b
NR: Not reported.
3-38
Terrestrial Organism Toxicity
Acute Oral (OPPTS Harmonized Guideline 850.2100), Dietary (OPPTS Harmonized
Guideline 850.2200; OECD Guideline 205), or Reproductive Toxicity (OPPTS Harmonized
Guideline 850.2300; OECD Guideline 206) in Birds
Conclusion:
No available acute oral, dietary, and reproductive toxicity data.
Basis for Conclusion:
No acute oral, dietary, or reproductive toxicity studies in birds were located.
Earthworm Subchronic Toxicity (OPPTS Harmonized Guideline 850.6200; OECD
Guideline 207)
Conclusion:
The available earthworm subchronic toxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
No earthworm subchronic toxicity studies were located. An acute (14-hour) LC50 of 130 mg/kg
soil and a NOEC of 100 mg/kg soil with the earthworm, Eisenia fetida (SafePharm, 1996), were
reported in IPCS 1998. However, the study has also been reported to be a 14-day subchronic
toxicity study (NICNAS, 2001). The study, or a study summary, was not available for an
independent evaluation of the study and the results.
3-39
Physical/Chemical Properties
Tris(1,3-dichloro-2-propyl) phosphate
CAS 13674-87-8
MF C9H15Cl6O4P
MW 430.91
SMILES ClCC(CCl)OP(=O)(OC(CCl)CCl)OC(CCl)CCl
Physical/Chemical Properties
Water Solubility:
Conclusion: The available water solubility data are adequate.
Basis for Conclusion: The key study (highlighted) was performed according to a reliable
method, and is in reasonable agreement with other values reported in the literature.
Solubility (mg/L) References
42 Akzo Nobel, 2001a,b: Water Solubility determination according to OECD Guideline
105 (shake-flask method)
7 Aston et al., 1996 (24/C); Hollifield, 1979; SRC, 2004 (PHYSPROP Database, 24/C);
HSDB, 2003 (24/C)
100 Eldefrawi et al., 1977; WHO, 1998 (30/C); Budavari, 2001 (The Merck Index); Lewis,
2000 (Sax's Dangerous Properties of Industrial Materials)
110 CERI, 1999
18.1 Confidential submitted study using shake flask method
Log Kow:
Conclusion: The available log Kow data are adequate.
Basis for Conclusion: The key study (highlighted) was performed according to a reliable
method.
Log Kow Reference
2.4 Akzo Nobel, 2001a,b: Determination of Octanol-Water Partition Coefficient
According to OECD Guideline 117 (HPLC Method)
3.8 WHO, 1998
3.65 SRC, 2004 (PHYSPROP Database); HSDB, 2003
3.75 Shake-flask method, Sasaki et al., 1981
3.69 Confidential submitted study using the HPLC method
3-40
Oxidation/Reduction: No data
Melting Point:
Conclusion: The available melting point data for TDCPP are adequate.
Basis for Conclusion: The key study (highlighted) was performed according to a reliable
method. It is noted that the other literature data do not agree with the key study; however, the
methods used to measure the melting points are not provided in any of the sources. As an
OECD-guideline compliant method, the key study is better described and better supported.
Melting Point (/C) References
-58 Akzo Nobel, 2001a,b: melting point determination by DSC (compliant with OECD
Guideline 102), freezing point was determined to be -40/C, melting point -58/C
27 CERI, 1999
26.66 Akzo Nobel, 2003
Boiling Point:
Conclusion: The boiling point data are adequate.
Basis for Conclusion: A variety of literature sources report the same value for the boiling point,
although there is some indication that the compound may decompose at or near the boiling point.
Since experimental details are not provided in any of the sources, it is not possible to determine
whether the temperatures reported are decomposition or boiling temperatures. Nevertheless,
given the high boiling point reported for this material, the available data are adequate to
characterize its potential volatility.
Boiling Point (/C/torr) References
236-237/5 SRC, 2004 (PHYSPROP database); Budavari, 2001 (The Merck Index);
Lewis, 2000 (Sax's Dangerous Properties of Industrial Materials);
WHO, 1998
200/4 Akzo Nobel, 2003
Dec. >200/4 WHO, 1998
Gradual Dec. >200 HSDB, 2003
Vapor Pressure:
Conclusion: The available vapor pressure data are not adequate
Basis for Conclusion: Although this measured vapor pressure is reported in two sources, it
appears to be very high relative to the boiling points reported for this chemical. For comparison,
an estimated vapor pressure (EPIWIN) is also included in the table below. The vapor pressure
remains a data need.
3-41
Vapor Pressure (torr//C) Reference
0.01/30 WHO, 1998; Akzo Nobel, 2001a,b
2.98 x10-7 EPIWIN, 2000; v. 3.11 estimate
Odor:
Conclusion: The odor of this compound has been adequately characterized.
Basis for Conclusion: Although no standardized tests are available for characterizing chemical
odors, the two descriptions found are similar, and are consistent with the low volatility expected
for this chemical.
Odor Reference
Mild Odor HSDB, 2003
Bland Odor Akzo Nobel, 2003
Oxidation/Reduction Chemical Incompatibility: No data
Flammability:
Conclusion: The flammability (as the flash point and autoignition temperature) has been
adequately characterized.
Basis for Conclusion: Studies on the flash point and autoingition temperature of this chemical
were located and appear reasonable given the other physical/chemical properties available for
this compound.
Flash Point Reference
252/C (coc) WHO, 1998; HSDB, 2003
>107.22/C (Seta closed cup) Akzo Nobel, 2003
Autoignition Temperature Reference
512.77/C Akzo Nobel, 2003
Explosivity: No data
Corrosion Characteristics: No data
3-42
pH:
This chemical does not contain functional groups expected to influence the pH of aqueous
solutions. Data for this endpoint are therefore not applicable.
UV/Visible Adsorption: No data
Viscosity:
Conclusion: The viscosity of this chemical at various temperatures has been adequately
characterized.
Basis for Conclusion: Studies on the viscosity of this chemical were located and appear
reasonable given the other physical/chemical properties available for this compound.
Viscosity (cP) Reference
1,800 at 25/C WHO, 1998; Akzo Nobel, 2003
2,200 at 0/C Akzo Nobel, 2003
540 at 40/C Akzo Nobel, 2003
Density/Relative Density/Bulk Density:
Conclusion: The density of this compound has been adequately characterized.
Basis for Conclusion: Consistent data are provided in several reputable sources.
Density Reference
1.52 at 25/C Specific gravity. WHO, 1998
1.5022 at 20/C Specific gravity. Budavari, 2001 (The Merck Index); Lewis, 2000 (Sax's Dangerous
Properties of Industrial Materials)
1.48 kg/L at 25/C Bulk density. HSDB, 2003
Dissociation Constant in Water:
This compound does not have functional groups that are expected to dissociate in water. This
endpoint is therefore not applicable.
Henry's Law Constant: No data
3-43
Environmental Fate
Bioconcentration
Fish:
Conclusion: The bioconcentration factor has been adequately characterized.
Basis for Conclusion: The two studies cited in the table below provide consistent information
for killifish under both static and flow-through conditions, over a variety of observation times,
and with varying initial concentrations of test substance. The BCF was also measured in
goldfish; the reported BCFs are independent of study length.
Key Design Parameters
Exp. Range Study
Reference Species BCF type (ppb) length T (/C) Comments
Sasaki et Killifish 113 Static 1,000 24 hours 25 Half-life for elimination
al., 1981 110 initial 55 hours of the test compound in
77 96 hours water + fish = 31 hours.
Sasaki et Goldfish 5 Static 1,000 24 hours 25 Half-life for elimination
al., 1981 3 initial 96 hours of the test compound in
water + fish = 42 hours.
Sasaki et Killifish 46? Flow- 400 3 days 25 BCF is independent of
al., 1982 through concentration; continuous
32? (all) 300 4 days (flow-through) results
correlate to static results
31? 40 6 days (Sasaki et al., 1981).
59?6 40 30 days
49?2 80 32 days
Daphnids: No data
Green Algae: No data
Oysters: No data
Earthworms: No data
Fish Metabolism:
Conclusion: The metabolism of TDCPP in fish is not adequately characterized in the literature.
Basis for Conclusion: The depuration rate is adequately described in killifish, however, the
metabolite distribution is not addressed.
3-44
Species Rate Comment Reference
Killifish Elimination half-life, 1.65 hours Depuration rate Sasaki et al., 1982
elimination of TDCPP
when exposed fish are
moved to clean water.
Killifish Apparent metabolism is much ~10% of applied TDCPP Sasaki et al., 1981
faster in killifish than in goldfish. remains in the water in
(Quantitative data are not the presence of killifish
provided.) after 96 hours. Control
(no fish) has no change in
TPP concentration.
Goldfish Apparent metabolism is much ~25% of applied TDCPP Sasaki et al., 1981
slower than in killifish. remains in the water after
(Quantitative data are not 96 hours in presence of
provided.) goldfish.
Degradation and Transport
Photolysis in the Atmosphere: No data
Photolysis in Water: No data
Photolysis in Soil: No data
Aerobic Biodegradation:
Conclusion: The biodegradation of TDCPP under aerobic conditions has been adequately
characterized.
Basis for Conclusion: The key study (highlighted) was performed according to a GLP-
compliant OECD guideline test. The other data located in the literature are generally in
agreement with the key study.
Study type/
Method Innoculum Acclim Degradation Time Comments Reference
OECD Activated 0% by CO2 28 days Initial concentrations Akzo Nobel,
Guideline sludge evolution. 2, 10 mg/L. GLP- 2001a,b; Akzo
301B compliant. Chemicals
Modified DOC red. not Also reported: Incorporated,
Sturm Test calculated 1) Closed bottle test 1990
due to (OECD Guideline
solubility 301D) showed no
issues. inhibition of bacterial
cultures in 10 days.
3-45
Study type/
Method Innoculum Acclim Degradation Time Comments Reference
Japanese Activated avg. 1% by 28 days Initial concentrations CERI, 1999;
MITI test sludge BOD 100 mg/L (test HSDB, 2003;
substance), 30 mg/L Chemicals
(sludge). Inspection and
Testing
Institute, 1992
OECD 302C 0% by O2 28 days WHO, 1998
uptake
River Die- Water from 7 days Initial concentrations WHO, 1998
Away Oh River 12.5% 14 days 20 mg/L in Oh River
(Osaka, 18.5% water and 1 mg/L in
Japan) Neya River water.
7 days Concentration in
Neya River 0% 14 days seawater not
(Osaka, 5.4% reported.
Japan)
Analysis by
7 days Molybdenum Blue
Seawater 0% 14 days calorimetric assay for
(Osaka Bay) 22% increase in phosphate
ion.
Anaerobic Biodegradation: No data
Porous Pot Test: No data
Pyrolysis:
Conclusion: The available pyrolysis data are not adequate.
Basis for Conclusion: Although a semi-quantitative description of the pyrolysis products is
given in the Choudry and Hutzinger paper, the list of degradates provided accounts for only 60%
of the total mass expected and doesn't contain any oxygenated or phosphorus-containing
compounds. Therefore, this study does not provide a complete profile of the pyrolysis of
TDCPP.
Pyrolysis Products Reference
Relative mol.% degradates, 0.1 mole TDCPP heated at 250-260/C under Choudhry and Hutzinger, 1982
reduced pressure (3 mm Hg), overall yield 60 wt%: trans-1,3
dichloropropene 26.7%, cis-1,3-dichloropropene 36.0%, 1,2,3
trichloropropane 34.4%, 1-chloro-2-propene 2.9%.
Thermal oxidative degradation in air at 370/C: Hydrogen halides, HSDB, 2003
halogenated C2 and C3 species, acrolein
3-46
Pyrolysis Products Reference
When heated to decomposition, it emits toxic fumes of Cl+ and POx Lewis, 2000 (Sax's Dangerous
Properties of Industrial Materials)
Hydrolysis as a Function of pH:
Conclusion: The hydrolysis rate data are adequate. The hydrolysis products are not described.
Basis for Conclusion: The studies cited below were GLP-compliant tests run according to
accepted guidelines.
T1/2 pH Temp. Comment Reference
>1 year 4 50/C OECD 111; EPA Ser. 835 OPPTS No. 835.2110. Akzo Nobel, 2001a,b
>1 year 7 GLP-compliant.
14.7 9 Initial concentration, 10 mg/L. Study length, 5
days days. Preliminary study.
28 days 9 40/C OECD 111; EPA Ser. 835 OPPTS No. 835.2110. Akzo Nobel, 2001a,b
GLP-compliant.
Definitive 30-day study.
128 9 20/C OECD 111; EPA Ser. 835 OPPTS No. 835.2110. Akzo Nobel, 2001a,b
days GLP-compliant.
Definitive 30-day study.
Sediment/Water Biodegradation: No data
Soil Biodegradation with Product Identification: No data
Indirect Photolysis in Water: No data
Sediment/Soil Adsorption/Desorption: No data
3-47
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stability of the flame retardant Fyrol FR-2. Bull. Environ. Contam. Toxicol. 21: 409-412.
Akzo Chemicals Incorporated. 1990. Letter from Akzo Chemicals Incorporated to USEPA
submitting enclosed reports on 2-propanol-(1,3-dichloro) phosphate and ethanol-(2-chloro)
phosphate with attachments. TSCA Section 8D Submission, OTS05028355.
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8). Original Submission to U.S. EPA HPV Challenge Program. (Robust summaries do not
identify the sources of unpublished studies.)
Akzo-Nobel, Inc. 2001b. Test plan and robust summaries for Fyrol FR-2 (CAS No. 13674-87
8). Revised Submission to U.S. EPA HPV Challenge Program. (Robust summaries do not
identify the sources of unpublished studies.)
Akzo Nobel. 2003. Akzo Nobel functional chemicals LLC. Fyrol FR-2 Material Safety Data
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Anderson, BT. 1990. Amgard TDCP: Acute inhalation toxicity study in rats. Inveresk Research
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(Volume I-IV). TSCA 8e submission by Stauffer Chemical Company (1981), OTS0204911.
[Published as Freudenthal and Henrich, 2000]
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(Volume V). TSCA 8e submission by Stauffer Chemical Company (1981), OTS0204911-1.
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3-48
Brusick, D; Matheson, D; Jagannath, DR; et al. 1979. A comparison of the genotoxic properties
of tris(2,3-dibromopropyl)phosphate and tris(1,3-dichloro-2-propyl)phosphate in a battery of
short-term bioassays. J. Environ. Pathol. Toxicol. 3: 207-226.
Budavari, S. (ed.). 2001. Fyrol FR-2. The Merck index - An encyclopedia of chemicals, drugs,
and biologicals. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc.
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