Indicators for lack of systemic availability of organic pigments.

Experimental data of all 143 organic pigments registered with the European Chemicals Agency, of which 88 were listed in a nanomaterial inventory, was retrieved from the registered substance fact sheets. Availability of the data was 93% for solubility, 82% for bacterial mutagenicity, 79% for acute oral toxicity, 75% for irritation, 59% for skin sensitisation, 36% for repeated dose toxicity and 34% for each clastogenicity and mutagenicity in mammalian cells and 23% for toxicity to reproduction. Pigments mostly had a water and octanol solubility of significantly below 0.1 mg/L, but fourteen were found to be of higher solubility. None were irritating to skin and eyes. Except for the metal salt and the ß-naphthol pigments, none of the insoluble pigments showed adverse effects up to limit doses indicating that poor solubility prevents systemic uptake of toxicologically relevant amounts. The few available toxicokinetic data shows absence of metabolism or significant uptake and is in support of this. Occasional effects observed on bacterial mutagenicity and skin sensitisation are attributed to impurities. There is no indication that for organic pigments other particle characteristics such as surface area or morphology have an impact on the investigated toxicological endpoints.

Phosphatidylethanolamine synthesis in the parasite mitochondrion is required for efficient growth but dispensable for survival of Toxoplasma gondii.

Toxoplasma gondii is a highly prevalent obligate intracellular parasite of the phylum Apicomplexa, which also includes other parasites of clinical and/or veterinary importance, such as Plasmodium, Cryptosporidium, and Eimeria. Acute infection by Toxoplasma is hallmarked by rapid proliferation in its host cells and requires a significant synthesis of parasite membranes. Phosphatidylethanolamine (PtdEtn) is the second major phospholipid class in T. gondii. Here, we reveal that PtdEtn is produced in the parasite mitochondrion and parasitophorous vacuole by decarboxylation of phosphatidylserine (PtdSer) and in the endoplasmic reticulum by fusion of CDP-ethanolamine and diacylglycerol. PtdEtn in the mitochondrion is synthesized by a phosphatidylserine decarboxylase (TgPSD1mt) of the type I class. TgPSD1mt harbors a targeting peptide at its N terminus that is required for the mitochondrial localization but not for the catalytic activity. Ablation of TgPSD1mt expression caused up to 45% growth impairment in the parasite mutant. The PtdEtn content of the mutant was unaffected, however, suggesting the presence of compensatory mechanisms. Indeed, metabolic labeling revealed an increased usage of ethanolamine for PtdEtn synthesis by the mutant. Likewise, depletion of nutrients exacerbated the growth defect (∼56%), which was partially restored by ethanolamine. Besides, the survival and residual growth of the TgPSD1mt mutant in the nutrient-depleted medium also indicated additional routes of PtdEtn biogenesis, such as acquisition of host-derived lipid. Collectively, the work demonstrates a metabolic cooperativity between the parasite organelles, which ensures a sustained lipid synthesis, survival and growth of T. gondii in varying nutritional milieus.