Toxicological Risks of Selected Flame-Retardant Chemicals (2000) / Chapter Skim
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18 Tetrakis(hydoroxymethyl) Phosphonium Salts
18 Tetrakis(hydoroxymethyl) Phosphonium Salts
Pages 417-439
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From page 417... ...
phosphonium salts have been used as flame retardants, the subcommittee chose to focus its assessment on THPC because it has a large toxicology database and is the most toxic of the phosphate salts. The subcommittee used the toxicity and exposure information on THPC to characterize the health risk from exposure to THPC.
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From page 418... ...
Phosphonium Chloride Properties Value Chemical formula C4Hl2O4PC Reference Structure CAS Registry # 124-64-1 Synonyms THPC Molecular weight 190.58 Physical state CH2OH 1 HOCH2—P—CH2OH I Cl CHtOH Crystalline solid; sold as 80% aqueous solution Color 80% aqueous solution is straw-colored or clear and colorless Solubility Vapor pressure pH Melting point Boiling point Density (water= 1) Soluble in water, methanol, ethanol; less Man 1 mg/rnL in DMSO, insoluble in ether, reaction with acetone 80% aqueous solution: 1.0 mm Hg at 25 °C 1 for aqueous solution of unspecified concentration; 2 for 80% aqueous solution 154°C 80% aqueous solution: 118°C 80% aqueous solution: 1.322 g/cm3 at 17.8°C; 1.34 g/cm3 at 20°C HSDB 1999 Loewengart and Van Duuren 1977 HSDB 1999 HSDB 1999 HSDB 1999 L\RC 1990; HSDB 1999 NTP 1991; Hazleton UK 1992 NTP 1991 NTP 1991 Hazleton UK 1991; Hazleton UK 1992 Grasseli and Ritchey 1975 NTP 1991 NTP 1991; Hazleton UK 1992
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From page 419... ...
Oral Acute, subchronic, and chronic toxicity studies in rats and mice provide indirect evidence that THPC is absorbed through the gastrointestinal tract and becomes systemically bioavailable (see Hazard Identification section)
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Moderate to severe skin reactions were observed in male white rats and rabbits treated topically for ~ ~ with 0.75 mL of 15%, 20%, or 30% aqueous THPC (Aoyama ~ 975~. In rats, skin redness was observed starting on ~ 4 for 2In this section, the subcommittee reviewed data on toxicity of tetrakis~hydroxymethyl)
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(1980) , citing the 1953 report by the Wisconsin Alumni Research Foundation, state that THPC is a mild skin irritant in the female rat and caused lethality, skin sloughing, and hyperemia after dermal application of >]
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From page 422... ...
Therefore, it is not possible to determine whether dermal exposure to THPC itself was the cause for the increased incidence of leukopenia in this study. Neurological Effects Mice treated with aqueous extracts from fabrics treated with a THPC-based FR became sluggish, had "reduced working capacity" for static work, and 2040% Tower cholinesterase activity levels (Afanas'eva and Evseenko 1971~.
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From page 423... ...
The authors did not comment on the significance of this finding, but the report notes that none of the 20 animals receiving no treatment with any compounds developed skin tumors over the 400 ~ experimental period. No tumors were observed in animals treated initially with extracts from THPC-treated cloth and then topically treated with the tumor promoter phorboT myristate acetate (PMA)
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From page 424... ...
Two of 10 males and one of 10 female rats died in the 15 mg/kg-d group, apparently due to Savage errors. Liver vacuolization was apparent in males at dose levels 27.5 mgA`g-d and in females 215 mg/kg-~.
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From page 426... ...
15 15 30 No effects at 3.75 mg/kg-d; Liver vacuolization in 8 of 10 M at 7.5 mg/kg-d; Liver vacuolization in 9 of 10 M, 8 of 10 F.; liver necrosis2 of minimal severity in 9 of 10 M, 7 of 10 F.; Liver vacuolization, necrosis in 10 of 10 M, F.; decreased body weight gain in M; Most died; paresis, incoordination, axonal degeneration; liver vacuolization 10/10 M, F liver necrosis in 7 of 10 M, 8 of 10 F No effects No effects Liver vacuolization in 10/10 M, F Liver vacuolization in 10/10 M, F.; necrosis in 10/10 M Most died, decreased weight gain; paresis, incoordination, axonal degeneration; liver vacuolization in 10/10 M, 9/10 F.; liver necrosis in 8/10 M, 7/10 F Rough hair coats, diarrhea; liver vacuolization in 9/50 M (c = 0/SO)
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From page 427... ...
had paresis and incoordination of the rear limbs as well as rough hair coats, hunched backs, diarrhea, lethargy, and axonal degeneration. Axonal degeneration was seen in 2 of 10 high-dose female rats and in at least ~ 9 of 20 high-dose mice and was characterized by swollen axon sheaths, missing or fragmented axons, and proliferation of neurolemma cells in the sciatic nerve, dorsal roots of the caudal spinal nerves, and spinal cord tracts.
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From page 428... ...
18 Red intestinal mucosa; Red intestinal mucosa; weight loss, decreased food intake; Red intestinal mucosa; weight loss decreased food intake, 1 death; increased post-implantation loss, decreased litter size, decreased fetal weight; fetuses had eye/limb malformation No effects; Hazleton Gastrointestinal irritation (1 animal) ; UK 1992 increased weight loss and fetal mal formations were not clearly treatment-related; One spontaneous abortion, increased weight loss and fetal malformation not clearly treatment-related One spontaneous abortion; decreased weight gain; decreased food intake; gastrointestinal irritation; one total resorption; eye fetal malformations in one litter F
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From page 429... ...
of THPC-treated fabric samples incubated inphysiological saline at 37°C for 18-24 hr (5 g fabric in 30 mL saline) also yielded negative results in Salmonella strains TA98, TA100, TAl537, and 1538, with or without exogenous metabolic activation (Huntingdon Research 1976~.
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~ 980~. THPC induced chromosome aberrations in CHO cells without metabolic activation using either a conventional or delayed harvest protocol ~ ~ ~ hr instead of ~ O fur)
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In the absence of relevant inhalation exposure data, the subcommittee chose to extrapolate inhalation RfCs from oral RfDs The subcommittee, however, recognizes that it is not an ideal approach and also recognizes that the estimated RfC levels might be considerably different than actual levels (if inhalation data were available)
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From page 432... ...
Liver toxicity occurred at the lowest dose tested in rats at 3.75 mg/kg-d which equates to 2.68 mg/kg-d when adjusted for discontinuous exposure (i.e., multiplied by 5/71. The LOAEL of 2.68 mg/kg-d for liver toxicity in the rat was divided by the composite uncertainty factor (UF)
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Noncancer Dermal Exposure Dermal exposure to THPC was estimated using the dermal exposure scenario described in Chapter 3. This exposure scenario assumes that an adult spends 1/4th of his or her time sitting on furniture upholstery treated with commercial THPC.
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Inhalation Exposure Particles Inhalation exposure estimates for THPC were calculated using the exposure scenario described in Chapter 3. This scenario assumes that a person spends 1/4th of his or her lifetime in a 30 m3 room containing 30 m2 of THPC-treated fabric and the room is assumed to have an air-change rate of 0.25/hr.
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From page 435... ...
Oral Exposure The assessment of noncancer toxicological risk for oral exposure to THPC is based on the oral exposure scenario described in Chapter 3. This scenario assumes a child is exposed to THPC by sucking on 50 cm2 of fabric treated with THPC, 1 fur/d for two yr.
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From page 436... ...
The subcommittee concluded that data are inadequate to determine human carcinogenic potential by the dermal route. Inhalation No adequate data are available in humans or laboratory animals to assess the carcinogenicity of THPC vapors or particles containing THPC.
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1971. Hygienic assessment of fireproof fabrics treated with an organophosphorus impregnating compound based on tetrahydroxymethylphosphonium chloride.
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phosphonium salts. Pp.95-107 in IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, Vol.48, Some Flame Retartdants and Textile Chemicals, and Exposures in the Textile Manufacturing Industry.
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From page 439... ...
1982. Neurotoxic evaluation of tetrakis hydroxymethyl phosphonium chloride in Fischer 344 rats.
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