tetracarboxyphenylporphine and tris(1-3-dichloro-2-propyl)phosphate

Organophosphate flame retardants (OPFRs) are used as replacements for the commercial PentaBDE mixture that was phased out in 2004. OPFRs are ubiquitous in the environment and detected at high concentrations in residential dust, suggesting widespread human exposure. OPFRs are structurally similar to neurotoxic organophosphate pesticides, raising concerns about exposure and toxicity to humans. This study evaluated the neurotoxicity of tris (1,3-dichloro-2-propyl) phosphate (TDCPP) compared to the organophosphate pesticide, chlorpyrifos (CPF), a known developmental neurotoxicant. We also tested the neurotoxicity of three structurally similar OPFRs, tris (2-chloroethyl) phosphate (TCEP), tris (1-chloropropyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP), and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), a major component of PentaBDE. Using undifferentiated and differentiating PC12 cells, changes in DNA synthesis, oxidative stress, differentiation into dopaminergic or cholinergic neurophenotypes, cell number, cell growth and neurite growth were assessed. TDCPP displayed concentration-dependent neurotoxicity, often with effects equivalent to or greater than equimolar concentrations of CPF. TDCPP inhibited DNA synthesis, and all OPFRs decreased cell number and altered neurodifferentiation. Although TDCPP elevated oxidative stress, there was no adverse effect on cell viability or growth. TDCPP and TDBPP promoted differentiation into both neuronal phenotypes, while TCEP and TCPP promoted only the cholinergic phenotype. BDE-47 had no effect on cell number, cell growth or neurite growth. Our results demonstrate that different OPFRs show divergent effects on neurodifferentiation, suggesting the participation of multiple mechanisms of toxicity. Additionally, these data suggest that OPFRs may affect neurodevelopment with similar or greater potency compared to known and suspected neurotoxicants.

Topics: Animals; Cell Culture Techniques; Cell Survival; Choline O-Acetyltransferase; DNA; Flame Retardants; Nerve Tissue Proteins; Organophosphates; Organophosphorus Compounds; Oxidative Stress; PC12 Cells; Phosphines; Porphyrins; Rats; Tyrosine 3-Monooxygenase

Restrictions on the use of polybrominated diphenyl ethers (PBDEs) have resulted in the increased use of alternate flame retardant chemicals to meet flammability standards. However, it has been difficult to determine which chemical formulations are currently being used in high volumes to meet flammability standards since the use of flame retardant formulations in consumer products is not transparent (i.e., not provided to customers). To investigate chemicals being used as replacements for PentaBDE in polyurethane foam, we analyzed foam samples from 26 different pieces of furniture purchased in the United States primarily between 2003 and 2009. Samples included foam from couches, chairs, mattress pads, pillows, and, in one case, foam from a sound-proofing system of a laboratory-grade dust sieve, and were analyzed using gas chromatography mass spectrometry. Fifteen of the foam samples contained the flame retardanttris(1,3-dichloro-2-propyl) phosphate (TDCPP; 1-5% by weight), four samples contained tris(1-chloro-2-propyl) phosphate (TCPP; 0.5 -22% by weight), one sample contained brominated chemicals found in a new flame retardant mixture called Firemaster 550 (4.2% by weight), and one foam sample collected from a futon likely purchased prior to 2004 contained PentaBDE (0.5% by weight). Due to the high frequency of detection of the chlorinated phosphate compounds in furniture foam,we analyzed extracts from 50 house dust samples collected between 2002 and 2007 in the Boston, MA area for TDCPP, TCPP, and another high volume use organophosphate-based flame retardant used in foam, triphenylphosphate (TPP). Detection frequencies for TDCPP and TPP in the dust samples were > 96% and were log normally distributed, similar to observations for PBDEs. TCPP was positively detected in dust in only 24% of the samples, but detection was significantly limited by a coelution problem. The geometric mean concentrations for TCPP, TDCPP, and TPP in house dust were 570, 1890, and 7360 ng/g, respectively, and maximum values detected in dust were 5490, 56,080 and 1,798,000 ng/g, respectively. These data suggest that levels of these organophosphate flame retardants are comparable, or in some cases greater than, levels of PBDEs in house dust. The high prevalence of these chemicals in foam and the high concentrations measured in dust (as high as 1.8 mg/g) warrant further studies to evaluate potential health effects from dust exposure, particularly for children.

Topics: Air Pollution, Indoor; Dust; Flame Retardants; Housing; Interior Design and Furnishings; Molecular Structure; Organophosphates; Organophosphorus Compounds; Porphyrins; United States