Pharmaceuticals and personal care products in Tunisian hospital wastewater: occurrence and environmental risk.

Despite concerns about the potential risk associated with the environmental occurrence of pharmaceuticals and personal care products (PPCPs), few studies address the emissions of hospitals to aquatic compartments. We examined within a 3-month sampling period the occurrence and environmental risk of PPCPs in seven Tunisian hospital wastewaters. From personal care products, UV filters, main metabolites, and benzotriazoles were quantified, with benzophenone 3 (oxybenzone, BP3) and benzotriazole (BZT) the most frequently found (71%) at median concentrations in the range 2.43 ± 0.87 ngL-1-64.05 ± 6.82 ngL-1 for BP3 and 51.67 ± 1.67 ngL-1-254 ± 9.9 ngL-1 for BZT. High concentrations were also found for 4-hydroxybenzophenone (4HB) (221 ± 6.22 ngL-1), one of the main metabolites of BP3. The antibiotics ofloxacin and trimethoprim, the anti-inflammatory acetaminophen, the antiepileptic carbamazepine, and the stimulant caffeine were present in all the wastewaters. The highest median concentration corresponded to acetaminophen, with 1240 ± 94 mgL-1 in Tunis Hospital, followed by ofloxacin with 78850 ± 39 µgL-1 in Sousse Hospital. For ecotoxicity assessment, acute toxicity was observed for Daphnia magna and Vibrio fischeri. The toxicity data were used in a hazard quotient (HQ) approach to evaluate the risk posed by the target PPCPs to aquatic organisms. The calculated HQs revealed that marbofloxacin (234 for V. fischeri), enrofloxacin (121 for D. magna), and BZT (82.2 for D. magna and 83.7 for V. fischeri) posed the highest risk, concluding that potential risk exists toward aquatic microorganisms. This study constitutes the first monitoring of UV filters in Tunisian hospital effluents and provides occurrence and toxicity data of PPCPs for reference in further surveys in the country.

Nanosized titanium dioxide UV filter increases mixture toxicity when combined with parabens.

To address the concern about the environmental impact of engineered nanoparticles frequently used in the recently marketed personal care and hygiene products (PCPs), we conducted a toxicity assessment and determined the EC50 values of the nanosized inorganic UV filter TiO2 (nano-TiO2), as well as those of the organic UV filter oxybenzone (BP3) and three parabens (methyl, propyl, and benzylparaben) present in most PCPs formulation. The bioassays were carried out through standardized toxicity bioassays on two environmentally relevant aquatic species i.e. Daphnia magna and Phaeodactylum tricornutum. For nano-TiO2 48 h EC50 on D. magna was 3.09 mgL-1 and for parabens ranged from 32.52 to 1.35 mgL-1. The two most toxic compounds on D. magna, nano-TiO2 and benzylparaben (BzP), were further tested with the algae. For nano-TiO2 72 h EC50 value was 2.27 mgL-1 and for BzP it was 10.61 mgL-1. In addition, D. magna was exposed to selected binary mixtures of the target compounds i.e. nano-TiO2+BP3, nano-TiO2+BzP and BP3+BzP On the endpoint of 48 h, a synergistic action was observed for nano-TiO2+BP3 and nano-TiO2+BzP, but an antagonistic effect occurred in the mixture BP3+BzP. These findings suggest that nano-TiO2 can increase the toxicity of the mixture when combined with other compounds.

Allergenicity of casein containing chalk in milk allergic schoolchildren.

BACKGROUND: Nondietary exposure to milk proteins may be a risk for children who do not outgrow milk allergy by school age. OBJECTIVE: To study the allergenicity of casein containing chalk. METHODS: A 6-year-old, milk allergic child developed asthma and rhinoconjunctivitis while in school. The suspected cause was dust-free chalk containing casein. To study the relationship of dust-free chalk containing casein with asthma and rhinoconjunctivitis, 13 additional milk allergic patients were studied: 3 school-aged children, 8 preschool-aged infants, and 2 children with outgrown milk allergy. Skin tests and/or specific IgE with chalk and casein were performed. A chalk use test was performed in older children. Milk allergens contained in chalk were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot, and IgE inhibition experiments. RESULTS: All school-aged, milk allergic children were exposed to chalk and reported symptoms attributed to chalk exposure. The skin test result to chalk was positive in 5 of 12 cases, and the specific IgE test result was positive in all 12 study participants in which it was performed. Casein strongly inhibited the binding of IgE to chalk. Chalk sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed proteins with molecular weight similar to caseins. Immunoblot demonstrated strong binding of IgE to chalk in a blurred pattern and a band at 30 kDa, inhibited by casein. The chalk challenge test result was positive in 2 school-age children who had a positive skin test result to chalk. Their symptoms improved after avoidance of chalk in the school. In 2 other cases in which the challenge test result was negative, chalk was reintroduced without problems. CONCLUSION: Inhalation of chalk dust containing casein can induce asthma symptoms in milk allergic patients. Hidden and nondietary sources of exposure should always be considered in food allergic patients.

Acute allergic reaction to an iron compound in a milk-allergic patient.

A child allergic to cow's milk developed a mild systemic allergic reaction after the first dose of Ferplex 40 (iron proteinsuccinylate). Skin tests and in vitro studies were performed in the child, in three cow's milk-allergic controls and in a non-allergic control. Milk, casein and iron proteinsuccinylate (Ferplex 40) were used for skin tests, specific immunoglobulin E (IgE) determination, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting and enzyme allergo sorbent test (EAST) inhibition. A review of the drug information sheet and contact with the manufacturer were also performed. Although proteinsuccinylate is indeed a succinylated casein (each dose containing about 575 mg of casein) there was no indication of the milk protein content in the prescribing information provided by the manufacturer. Skin tests and specific IgE were positive in the case and in all allergic controls, except for EAST to iron proteinsuccinylate in one control. In EAST, iron proteinsuccinylate in solid phase was 100% inhibited by casein and casein in solid phase was inhibited 74% by iron proteinsuccinylate. SDS-PAGE of iron proteinsuccinylate showed a broad 46 kDa band and a blur of aggregated material. On immunoblot, the patient's IgE reacted to this heavily aggregated material and in the native casein extract recognized a 35-kDa band. The allergenicity of succinylated casein (proteinsuccinylate) among milk-allergic children is demonstrated. The protein source used in drug-protein conjugates should always be indicated by the manufacturer (as it should be in foods) to avoid potential risks to allergic patients.