Toxicological Risks of Selected Flame-Retardant Chemicals (2000) / Chapter Skim
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17 Aromatic Phosphate Plasticizers
17 Aromatic Phosphate Plasticizers
Pages 387-416
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From page 387... ...
TCP was chosen as the representative aromatic phosphate ester flame retardant for risk assessment because it has the most complete toxicity database. The subcommittee used that information to characterize the health risk from exposure to TCP.
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Chemical Fonnula Structure CAS Registry # Synonyms 388 TO~7COLOGICAL RISKS OF SELECTED FLAME-RETARDANT CHEMICALS TABLE 17-l Physical and ChemicalProperties for Tricresyl Phosphate (TCP) , Mixed Isomers Properties Value C2lH2lO4P Reference HSDB 1999 o ~CH3 1330-78-5 Tritolyl phosphate; trimethylphenyl phosphate; phosphoric acid, tritolyl ester; phosphoric acid, tris~methylphenyl)
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Additional details were not provided. Inhalation No studies were identified that have investigated the absorption of TCP in humans or laboratory animals following inhalation exposure.
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It is not known if the patterns of distr~bution for TOCP and metabolites can be generalized to other TCP isomers. Inhalation No studies were identified that investigated the distribution of TCP in humans or laboratory animals following inhalation exposure.
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However, there are no data to suggest that TMCP or TPCP is metabolized to neurotoxic metabolites. Exposure to TCP mixtures containing isomers with one or two ortho-creso} groups could result in the for~nation of neurotoxic metabolites (Iohnson 1975; NTP 1994~.
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Inhalation No studies were identified that investigated the excretion of TOP in humans or laboratory animals following inhalation exposure. Oral Excretion of radioactivity following oral administration of t4C-TMCP, ~4CTPCP, or i4C-ToCP in rats at doses of 0.5 (~4C-TMCP and i4C-TPCP only)
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tin this section, the subcommittee reviewed toxicity data on aromatic phosphate plasticizers, including the toxicity assessment prepared by the U.S. Consumer Product Safety Commission (Ferrante 1999~.
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Other Effects No studies were identified that investigated the immunological, or reproductive, developmental, or carcinogenic effects of TCP following dermal exposure. Inhalation Exposure Systemic and Neurological Effects Only one study was located that investigated the toxicity of TCP in humans following inhalation exposure.
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Oral Exposure Systemic Effects NTP (1994) conducted ~ 6-d gavage studies, ~ 3-wk gavage and feed studies, and 2-yr feed studies of a commercial TCP mixture in rats and mice.
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397 cry ~ act Go - - - ~ oo ~ ~ ~ 'e .
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Terminal body weights were significantly reduced in mate rats and mice at 2200 mg/kg-d, and female mice at 2400 mg/kg-~. Decreased hindlimb grip strength was noted in female rats at 2400 mg/kg-d and various neurological parameters were considered abnormal at 2200 mg/kg-d in both male and female mice.
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Hindlimb grip strength was significantly reduced in female mice in the 250 ppm group in the 3-mo evaluation, but notin the subsequent evaluations. Serum cholinesterase was significantly reduced in a dose-relatedmanner in both mares and females at 2 60 ppm at all time points.
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were significantly reduced at ~ 00 ppm TCP while leucocyte and macrophage migration was inhibited at 50 and 100 ppm TCP. Although the results of this study suggest that the immune system may be a sensitive target for TCP, the study included only limited assessment of immune function and the test material was not well characterized.
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with lubricating oil, mineral oil, hydraulic fluid, or some similar material containing TCP. The first symptom of delayed neuropathy in affected persons, occurring 3-28 ~ after exposure, is sharp, cramp-like pain in the calves (IPCS 1990~.
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Male and female mice were fed diets containing PRO, 0.05°/O, 0.~°/O, or 0.2% TCP ~ 79% tricresyl phosphate esters, including 21% TMCP, 4% TPCP, and <0. i% TOCP, and I 8% dicresyl phosphate esters)
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Decreased body weights were observed in females from both dose groups and decreased testis and epididymis weight in males of the 0.~% group. Decreased sperm motility and increased abnormal sperm was observed in mates in both dose groups.
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lipidosis and hypertrophy of adrenocortical cells in rats of both sexes and ovarian interstitial cells in females, and degeneration of the seminiferous tubules in mates. These lesions all occurred within 20 ~ of exposure and progressed as exposure continued.
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Additional details regarding this study were unavailable. QUANTITATIVE TOXICITY ASSESSMENT Quantitative toxicity assessments of aromatic phosphate esters was estimated using toxicity data for TCP.
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The subcommittee identified the adrenal gland and ovarian lesions in female rats and adrenal and liver lesions in female mice that occurred at 7 mg/kg-d to be the key critical effect for deriving an oral RfO for TCP. Application of a composite uncertainty factor (UF)
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Therefore, the weight-of-evidence classification from the oral data is expected to apply for dermal exposure as well. Inhalation No studies were located that investigated the carcinogenicity of TCP in humans or animals following inhalation exposure.
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, reference dose; UFA, uncertainty factor for ~nterspecies variability to humans; UFH, uncertainty factor for ~n~aspecies variability. EXPOSURE ASSESSMENT AND RISK CHARACTERIZATION Noncancer Dermal Dermal exposure to TCP was estimated using the dermal exposure scenario described in Chapter 3.
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Using Equation 3 in Chapter 3 and the alternate Kp, the dermal daily dose rate for TCP was estimated to be 3.0 x 10-3 mg/kg-~. In the absence of a dermal Ri D, the subcommittee believes it is appropriate to use the oral RfD for TCP Of 7 x 10-2 mg/kg-d as the best estimate ofthe internal dose from dermal exposure.
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has used this approach when inhalation exposure data were insufficient to derive inhalation exposure levels. The subcommittee believes that such an approach is justified for conservatively estimating the toxicological risk from exposure to Fits, and the derived RfC value should be used as an interim or provisional level until relevant data become available for the derivation of an inhalation RfC.
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Division ofthe short-term inhalation vapor exposure concentration of 0.417 mg/m3 by the provisional RfC of 0.245 mg/m3 yields a hazard index of I.7, which indicates that inhalation exposure at the worst-case levels might pose a noncancer risk. Oral Exposure The assessment of noncancer toxicological risk for oral exposure to TCP is based on the oral exposure scenario described in Chapter 3.
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Therefore, TCP is not anticipated to cause cancer in humans from oral exposure to treated furniture upholstery.
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Lamb,4th.1988. Reproductive toxicity oftricresyl phosphate in a continuous breeding protocol in Swiss (CD-1)
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1993. Pathogenesis of cholesterol lipidosis of adrenocortical and ovarian interstitial cells in F344 rats caused by tricresyl phosphate and butylated triphenyl phosphate.
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The toxicity of certain aromatic phosphate esters. University of Cincinnati, Wright Air Development Center.
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