Toxicological Risks of Selected Flame-Retardant Chemicals (2000) / Chapter Skim
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14 Organic Phosphonates
14 Organic Phosphonates
Pages 307-337
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From page 307... ...
tin this chapter, the toxicity data were discussed for DMHP because most of the relevant data for organic phosphates were available for this compound.
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From page 308... ...
, Bis~hydroxymethyl) phosphine oxide; dimethoxyphosphine oxide; dimethylhydrogenphosphite; dimethyl phosphite; dimethyl acid phosphite; 0,0'dimethyl phosphonate; dimethyl phosphorous acid; DMHP; hydrogen dimethyl phosphite; methyl phosphonate; NCI-C54773; phosphoric acid dimethyl ester; phosphorous acid dimethyl ester; TL 585 110.05 Mobile liquid Solubility in water = 1 x 106 mg/L; miscible in most organic solvents; soluble in pyr~m~dine Color Colorless Vapor pressure log Kow 4.52 mm Hg at 25°C -1.13 pH Not available Melting Not available point Boiling 170.5 °C point Flash point 96 °C Reference Howard and Meylan 1997 NTP 1985 Howard and Meylan 1997 IARC 1990; NTP 1985; HSDB 1999 Howard and Meylan 1997 Hawley 1981; as cited in L\RC 1990 Howard and Meylan 1997; CRC Press 1992 Hawley 1981; as cited in IARC 1990 Howard and Meylan 1997 Howard and Meylan 1997 Howard and Meylan 1997 Hawley 1981, as cited in IARC 1990 (CorltinuedJ
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From page 309... ...
Dermal LDso studies suggest that DMHP is systemically available following dermal application. Inhalation Exposure No data describing toxicokinetics of DMHP from the inhalation route were identified during the course of this review.
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From page 310... ...
It exhibited systemic effects of depression, ptosis, 2In this section, the subcommittee reviewed toxicity data on organic phosphonates, including the toxicity assessment prepared by the U.S. Consumer Product Safety Commission (Hatlelid 1999~.
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Other Systemic Effects No data were found regarding the immunological, reproductive, developmental, or carcinogenic effects of DMHP following dermal exposure. Inhalation Exposure A summary of the inhalation toxicity data of DMHP is presented in Table 14-2.
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From page 312... ...
312 au · _ o on a' · _4 o Cal C)
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From page 313... ...
According to Bio/dynamics (1980) , reduced body weights at the higher exposure levels somewhat obscured the increase in absolute and relative kidney weights.
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From page 314... ...
In the ~ 3-wk study in rats, the NOAEL for DMHP was determined to be ~ 00 mg/kg-d based on body weight depression in female rats. In the ~03-wk study, dose-related histopathological changes were observed in tissues ofthe lung, forestomach, eye, cerebellum, and hematopoietic system.
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From page 315... ...
o .s to a an o cd o os I, cd so - ~ EM c)
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This effect was not observed in any other treatment group of male or female rats and was not noted in the B6C3F, mice. Reproductive and Developmental Effects No data on reproductive and developmental toxicity of DMHP were located.
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From page 319... ...
At a dose of 100 mg/kg, alveolar/bronchiolar carcinomas occurred in one of 50 animals while none occurred among 50 vehicle controls. There was also a dose-related increase in the incidence of squamous cell carcinomas in the lungs of the male rats (O of 50 in vehicle control, O of 50 at 100 mg/kg, 5 of 50 at 200 mg/kg; p = 0.020, life table test)
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Female rats displayed a significant (p < 0.05) positive trend for alveolar-bronchiolar carcinoma, but the high-dose effect was not found to be statistically significant when compared to controls.
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323 o Cal '0 ~ ~ en ;, Ct _ ~ ._ V)
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~ 987~. Mouse bone marrow micronucleus tests revealed a positive, but not significant, increasing trend in percentage of micronucleated, polychromated erythrocytes (Shelby et al.19934.
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From page 325... ...
TABLE 14-5 Oral Reference Dose for Dimethyl Hydrogen Phosphite RfD (mg/kg-d) Critical effect Species 0.12 Increases~nhyperpla- Female sia in the lung (alveo- rats tar epithelium hyperplasia, a de no matou s Effect level Uncertainty (mg/kg-d)
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From page 326... ...
There was also a significantly increased incidence of mononuclear cell leukemia in male rats exposed to DMHP at a dose of 100 mg/kg-d,5 d/wk, for 103 wk as compared to the vehicle controls (NTP 19854. An increased incidence of alveolar/bronchiolar carcinomas occurred in female F-344/N rats exposed to DMHP at dose levels of 50 or 100 mg/kg-d for 5 dJwk, for 103 wk.
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From page 327... ...
Therefore, the subcommittee used the oral cancer SF of 5.4 x 10~3/mg/kg-d for calculating cancer risk estimates for DMHP EXPOSURE ASSESSMENT AND RISK CHARACTERIZATION Noncancer Dermal Exposure Dermal exposure to DMHP was estimated using the dermal exposure scenar~o described in Chapter 3. This exposure scenario assumes that an adult spends 1/4th of his or her time sitting on furniture upholstery backcoated with DMHP and also assumes 1/4th of the upper torso are is in contact with the upholstery and clothing presents no barrier.
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From page 328... ...
328 CO ._ v a' au U
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So 8 ~ ~ ~4 Cal ~ ~ a~ ~ c~ 3 ~ 3 o ~ o ~: o ~ U. ~ o o ._ ~ ._ Ct ·— Cd ~ 3 :: C)
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From page 330... ...
In the absence of a dermal Rfl) , the subcommittee believes it is appropriate to use the oral RfD for DMHP of 0.12 mg/kg-d as the best estimate of the internal dose from dermal exposure Using Equation 3 in Chapter 3 and the alternate KP, the dermal daily dose rate for DMHP was estimated to be 11.4 mg/kg-~.
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From page 331... ...
The time-averaged exposure concentration for particles was calculated using Equation 6 in Chapter 3. in the absence of relevant inhalation exposure data, the subcommittee chose to estimate inhalation RfCs from oral RfDs.
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Cancer Dermal Human cancer risk from dermal exposure to DMHP was calculated by multiplying the oral cancer potency factor for DMHP by the most conservative
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From page 333... ...
An inhalation cancer potency value was not available for DMHP, therefore a provisional inhalation cancer potency value of 1.54 x 10~6/pg/m3 was derived from oral cancer potency data for DMHP. Multiplication of the exposure estimates of 0.725 ,ug/m3 for particulate times the provisional cancer potency value yields an estimated lifetime cancer risk of I.1 x lo-6 and suggests that the cancer risk associated with the inhalation of DMHP particulates is negligible at the given upholstery concentrations and the exposure parameters in the worst-case exposure scenario.
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Using Equation ~ 6 in Chapter 3, the lifetime average dose rate for DMHP by the oral exposure route was calculated to be I.7 x i0-3 mg/kg-~. Lifetime cancer risk for this exposure scenario was then estimated by multiplying the oral lifetime daily dose rate times the oral cancer potency factor for DMHP of 5.4 x 10~3/mg/kg-d yielding a cancer risk estimate of 9.
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From page 335... ...
Cancer potency slope factors were available for oral and inhalation. Because DMHP is soluble in water, there is concern about noncancer effects after dermal absorption and concern about cancer risk by all three routes of exposure.
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From page 336... ...
Medford, Assistant Executive Director for Hazard Identification and Reduction, Subject: Toxicity Review for Organic Phosphonates and Cyclic Phosphonate Esters, March 25, 1999.
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From page 337... ...
1988. Pathological end biochemical effects of dimethyl hydrogen phosphite in Fischer 344 rats.
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