Acute LC Research Articles

Interferon gene expression declines over time post-COVID infection and in long COVID patients

Background Interferons (IFNs) represent a first-line defense against viruses and other pathogens. It has been shown that an impaired and uncontrolled release of these glycoproteins can result in tissue damage and explain severe progression of coronavirus disease 2019 (COVID-19). However, their potential role in Long-COVID syndrome (LC) remains debateable. Objectives The objective of the present study is to shed further light on the possible role of IFNs (and related genes) gene expression patterns in the progression of COVID-19 and LC patients. Methods We carried out a multi-cohort study by analyzing the IFN gene expression patterns (using different IFN gene signatures) in five cohorts of acute COVID-19 (n = 541 samples) and LC patients (n = 188), and compared them to patterns observed in three autoimmune diseases (systemic lupus erythematous [n = 242], systemic sclerosis [n = 91], and Sjögren’s syndrome [n = 282]). Results The data show that, while the interferon signatures are strongly upregulated in severe COVID-19 patients and autoimmune diseases, it decays with the time from symptoms onset and in LC patients. Differential pathway analysis of IFN-related terms indicates an over activation in autoimmune diseases (IFN-I/II) and severe COVID-19 (IFN-I/II/III), while these pathways are mostly inactivated or downregulated in LC (IFN-I/III). By analyzing six proteomic LC datasets, we did not find evidence of a role of IFNs in this condition. Conclusion Our findings suggest a potential role of cytokine exhaustion mediated by IFN gene expression inactivation as a possible driver of LC.

Comparative Assessment of Cadmium and Copper Toxicity to Physa acuta (Draparnaud, 1805).

Cadmium and copper toxicity was investigated using bioassays with neonates of a freshwater gastropod Physa acuta. Mortality, lethal time, and effects on shell length were studied during 28-day chronic exposure experiments. Relative toxicity was assessed from acute and chronic LC values. Copper showed significantly more toxicity at lower concentrations than cadmium ([Formula: see text] < 0.001), causing mortality at the same response levels. Conversely, cadmium affected shell length at lower concentrations than copper, although no significant differences ([Formula: see text] > 0.05) were found in affected shell length between copper and cadmium at the end of the assays. Lethal time (LT[Formula: see text]) was significantly affected by metal concentration ([Formula: see text] < 0.001), with a reduction of 8.28% and 5.90% in time per 0.001 mg/L increase of copper and cadmium, respectively. Physa acuta neonates showed medium to high sensitivity to cadmium and copper compared to other freshwater gastropod species, showing it is a suitable test organism, particularly for chronic ecotoxicological assessment.

Changes in biochemical parameters of freshwater fish Labeo rohita exposed to lethal and sub-lethal concentrations of indoxacarb

The Indian major carp Labeo rohita (Hamilton) was exposed to the new generation pesticide Indoxacarb for 24, 48, 72 and 96 h and the acute static LC 50 values were determined as 0.0589, 0.05669, 0.05522 and 0.0531 respectively. These LC50 values indicate that the indoxacarb is highly toxic to fish. The fish were exposed to sub-lethal concentration (1/10 th 96 h LC 50 ) for 8 days and the changes in the biochemical constituents of the vital organs viz, Gill, Liver, Brain, Muscle, and Kidney were studied. Significant changes in these organs of fish were observed. The changes were noted as tissue specific and time dependent. Several behavioral changesduring the period of exposure were also observed and noted. The results obtained were discussed at length with the available literature.

Characterization of S Gene Region Among HBV-infected Patients from Orissa

© 2011, INASL 12 Characterization of S Gene Region Among HBV-infected Patients from Orissa R Panigrahi*, A Biswas*, MK Panigrahi**, A Pal*, M Bandopadhyay*, SP Singh**, HS Das**, S Chakrabarti†, R Chakravarty* *ICMR Virus Unit, Kolkata, ID and BG Hospital Campus, Kolkata **SCB Medical College, Cuttack, Orissa †National Institute of Cholera and Enteric Diseases, Kolkata, India Background: Genetic mutation might account for the presence of hepatitis B virus (HBV) DNA among liver disease individuals. The aim of this work was to describe the clinical characteristics associated with the HBV genotypes circulating in south-eastern India. Materials: A total of 36 HBsAg patients were included in the study. Surface gene regions were amplified by PCR for detection of HBV infection and surface gene was analyzed after direct sequencing. Analysis of MHR region was analyzed by using the BLOSUM scores. Results: HBV genotypes observed in HBV-infected patients were as follows: 8 patients with genotype A (22.2%), 1 with C (2.7%), 27 with D (75.0%). Male patients predominated in this study (91.6%). Among the 18 patients infected with sub-genotype D5, a considerably higher prevalence was found among LC patients (55.5%), CHB patients (27.7%), and acute patients (16.6%). No prevalence of HBV/D2 was found in the present study. The distribution of MHR mutations among the clinical groups was found in acute patients (0%), CHB patients (10%), and LC patients (17.6%). Conclusion: HBV sub-genotypes D5 were found in a significant proportion in our study population as compared with other parts of India. Interestingly, HBV D5 was found to be more frequently associated with liver cirrhosis than other clinical groups. Mutations in the immunodominant domains of S gene were found to increase with increasing disease severity. Thus our study will add to the knowledge of HBV genotype distribution and characterization in India. Conflict of Interest: None 03_JCEH-Abstract.indd 12 3/18/2011 11:13:03 AM

Can the Biotic Ligand Model Predict Cu Toxicity Across a Range of pHs in Softwater-Acclimated Rainbow Trout?

This study examined the effects of pH (5.0-8.5) on the toxicity of waterborne Cu to juvenile rainbow trout (Oncorhynchus mykiss) in soft water under flow-through conditions. Relationships between 96 h or 30 day Cu toxicity and 24 h lethal Cu accumulation on the gills (24 h LA(50-Acute) or 24 h LA(50-Chronic)) were examined in the context of predictions made using the biotic ligand model (BLM). Acute toxicity was relatively constant across pHs except for a 2- to 3-fold higher LC(50) at pH 5.0. In the chronic exposure, the fish had similar tolerance to Cu from pH 5.0 to 8.0, but were 3- to 4-fold more tolerant at pH 8.5. This pattern was not captured by the current BLM which predicts that acute and chronic LC(50) values should increase progressively from pH 5.0 to 8.5, with much greater values than those observed at the higher pH range. BLM-based water quality criteria would not be protective for trout at pH 8.0 or 8.5 in acute exposure to Cu in soft water. The measured 24 h LA(50-Acute) and LA(50-chronic) at pH 8.5 were higher, and 24 h LA(50-Chronic) at pH 5.0 was lower than those at the other pHs. This study indicates that gill Cu bioaccumulation does not explain toxicity at high or low pH, and the BLM needs revision to adequately predict Cu toxicity to trout in soft water.

Long chain n − 3 PUFA-rich meal reduced postprandial measures of arterial stiffness

The consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) is known to be cardio-protective. Data on the influence of LC n-3 PUFA on arterial stiffness in the postprandial state is limited. The aim of this study was to investigate the acute effects of a LC n-3 PUFA-rich meal on measures of arterial stiffness. Twenty-five healthy subjects (12 men, 13 women) received a control and a LC n-3 PUFA-rich meal on two occasions in a random order. Arterial stiffness was measured at baseline, 30, 60, 90, 120, 180 and 240 min after meal consumption by pulse wave analysis and digital volume pulse to derive an augmentation index and a stiffness index respectively. Blood samples were taken for measurement of lipids, glucose and insulin. Consumption of the LC n-3 PUFA-rich meal had an attenuating effect on augmentation index (P=0.02) and stiffness index (P=0.03) compared with the control meal. A significant treatment effect (P=0.036) was seen for plasma non-esterified fatty acids concentrations. These data indicate that acute LC n-3 PUFA-rich meal consumption can improve postprandial arterial stiffness. This has important implications for the beneficial properties of LC n-3 PUFA and cardiovascular risk reduction.

Toxicity of selected pesticides to freshwater shrimp, Paratya australiensis (Decapoda: Atyidae): Use of time series acute toxicity data to predict chronic lethality

Toxicity of six pesticides (carbaryl, chlorpyrifos, cypermethrin, dimethoate, diuron and fenarimol) to the freshwater shrimp, Paratya australiensis was assessed after 96 h exposures. Of the six pesticides tested, alpha cypermethrin was the most toxic to the shrimp followed by chlorpyrifos, carbaryl, dimethoate, fenarimol and diuron. Regression methods for predicting chronic toxicity (lethality) from acute lethality data with shrimp were developed and compared, and it was found that the log–log model gives the most reliable predictions of the probability of death as a function of extended exposure times. Based on this model, chronic toxicity (21 days) to P. australiensis was estimated as 0.0058 μg/L for alpha cypermethrin, 4.9 μg/L for carbaryl, 0.004 μg/L for chlorpyrifos, 89 μg/L for dimethoate, 240 μg/L for diuron and 1500 μg/L for fenarimol. Acute LC 10 values were also useful predictors of the chronic lethality. The log–log model was used to derive extrapolated chronic values that were compared to measured experimental chronic values for two fish species. The predictions of chronic toxicity based on acute toxicity data were found to give credible results for both fish species. These predictions of chronic toxicity can therefore be used in ecological risk assessments to fill in gaps with reasonable confidence where no measured estimates of chronic toxicity are available.

The mysid Siriella armata as a model organism in marine ecotoxicology: comparative acute toxicity sensitivity with Daphnia magna

Siriella armata (Crustacea, Mysidacea) is a component of the coastal zooplankton that lives in swarms in the shallow waters of the European neritic zone, from the North Sea to the Mediterranean. Juveniles of this species were examined as standard test organisms for use in marine acute toxicity tests. The effects of reference toxicants, three trace metals (Copper, Cadmium and Zinc), and one surfactant, sodium dodecyl sulfate (SDS) were studied on S. armata neonates (\24 h) reared in the laboratory. Acute toxicity tests were carried out with filtered sea water on individual chambers (microplate wells for metals or glass vials for SDS) incubated in an isothermal room at 20 degrees C, with 16 h light: 8 h dark photoperiod for 96 h. Each neonate was fed daily with 10-15 nauplii of Artemia salina. Acute (96 h) LC50 values, in increasing order, were 46.9 lg/L for Cu, 99.3 lg/L for Cd, 466.7 lg/L for Zn and 8.5 mg/L for SDS. The LC(10), NOEC and LOEC values were also calculated. Results were compared with Daphnia magna, a freshwater cladoceran widely used as a standard ecotoxicological test organism. Acute (48 h) LC(50) values were 56.2 lg/L for Cu, 571.5 lg/L for Cd, 1.3 mg/L for Zn and 27.3 mg/L for SDS. For all the reference toxicants studied, the marine mysid Siriella armata showed higher sensitivity than the freshwater model organism Daphnia magna, validating the use of Siriella mysids as model organisms in marine acute toxicity tests.

Toxicity Test of Ethanol Extract Ant Plant Local Aceh (Mymercodia sp) Method of BSLTLarvae Shrimp Artemia salina Leach

Toxicity test and phytochemical screening of ant plant ethanol extract were done. The toxicity test was done by employing the Brine Shrimp Lethality Test (BSLT) method. Sample of ant plant taken from the Aceh Besar forest have been extracted with ethanol. The sample was thenconcentrated using a rotary evaporator until a crude extract was obtained. The extract was tested by toxicity to larva Artemia salina L. Thetoxicity test for larvae Artemia salina Leach have been done by employing the Brine Shrimp Lethality Test (BSLT) method at four concentrationlevels, i.e: 250 ppm, 125 ppm, 50 ppm, and 25 ppm. The result of the research showed that ethanol extract of ant plant Aceh had acute toxicityby LC value 61.11 ppm. The extract had identified were fenolik, saponin, steroid and terpenoid.____________________________________________________________________________________________________________________Key words: rine Shrimp Lethality Test, LC5050, Ant Plant, Aceh, Bphytochemical Screening

Potential of 11 Pesticides to Initiate Downstream Drift of Stream Macroinvertebrates

Downstream drift of lotic macroinvertebrates induced by toxicants is a well-known ecologically relevant phenomenon. However, little is known about which toxicants can initiate drift, and potential drift-initiating effects of contaminants are not taken into account in ecotoxicological risk assessment. The aim of the present study was to evaluate potential drift-initiating action of 11 pesticides having different target groups and modes of action. Sublethal concentrations of the pesticides were tested in stream microcosms with amphipods (Gammarus pulex), blackfly larvae (Simulium latigonium), and mayfly larvae (Baetis rhodani). The results show that 6 out of 11 pesticides tested can initiate drift of macroinvertebrates at sublethal concentrations 7-22 times lower than acute LC(50)s (thiacloprid, imidacloprid, acetamiprid, iprodione, fenvalerate, and indoxacarb). All the toxicants that exhibited drift-initiating action are neurotoxic insecticides belonging to the groups of pyrethroids and neonicotinoids except the fungicide iprodione. The pesticides that did not initiate drift are fungicides (cyprodinil, prochloraz, and azoxystrobin), a juvenile-hormone mimic (fenoxycarb), and a pyrazole insecticide (tebufenpyrad) affecting cell energy production. Remarkably, for all the drift-initiating toxicants, drift of the tested animals was detected within 2 h after contamination. This shows that macroinvertebrate drift can be induced even by short-term pulse exposures to neurotoxic insecticides, at field-relevant concentrations. The present results imply that the possibility of drift-initiating effects of pesticides should be considered within the risk assessment framework for pesticides, as all neurotoxic substances that were investigated did initiate drift at sublethal concentrations.

Abstract 1368: BK Channel β1 Subunits Are Specific Effectors Of Cholane-induced Channel Activation

The activity of large conductance, Ca 2+ - and voltage-gated potassium (BK) channels in smooth muscle critically controls vascular tone. Depolarization-induced Ca 2+ -entry in the myocyte activates BK channels, which generate outward positive current that tends to repolarize the membrane, limit Ca 2+ entry and, thus, oppose contraction. Cholane-derived steroids (e.g., lithocholic acid, LC) reduce vascular tone in isolated, resistance-size rat cerebral arteries by selective activation of myocyte BK channels. In most tissues, native BK channels consist of pore-forming α (encoded by KCNMA1 or Slo1 ) and accessory β1–4 (encoded by KCNMB1–4 ) subunits. Remarkably, KCNMB expression is tissue-specific: while KCNMB1 is highly predominant in smooth muscle, KCNMB2–4 are not. Thus, agents that target BK β1 subunits may be used to selectively modulate myocyte BK channel function. After cloning the BK α subunit from rat cerebral artery myocytes (termed “cbv1”, AY330293 ), we demonstrated that homomeric cbv1 channel steady-state activity (NPo) was not affected by acute LC application. In contrast, heteromeric cbv1+β1 channel NPo was reversibly increased by LC (+290% of control at EC max ~150 μM; EC 50 =46 μM). Whether the other BK β subunits (2–4) can substitute for β1 to evoke LC-sensitivity in the BK channel remains unknown. To test this, we applied 150 μM LC to the intracellular side of inside-out patches excised from Xenopus laevis oocytes expressing cbv1 alone or cbv1 with a given BK β subunit subtype (1–4). Currents were evoked with the membrane clamped at ±20mV and free Ca 2+ i set to 10 μM, a concentration found in the cerebral artery myocyte during contraction. As previously found, LC consistently failed to increase homomeric cbv1 NPo, while drastically enhancing heteromeric cbv1+β1 channel NPo. Remarkably, LC failed to activate cbv1+β2, cbv1+β3 and cbv1+β4 heteromeric channels. In conclusion, the BK β1 (smooth muscle-type) subunit serves as a unique sensor for cholane-derived steroids. Thus, these compounds provide a platform for designing therapeutic agents to treat cardiovascular disease where reduction of vascular tone is required.

Derivation of predicted no effect concentrations (PNEC) for marine environmental risk assessment: Application of different approaches to the model contaminant Linear Alkylbenzene Sulphonates (LAS) in a site-specific environment

Four sediment-dwelling marine organisms were exposed to sediments spiked with increasing concentrations of Linear Alkylbenzene Sulphonate (LAS). The selected endpoint mortality was reported daily and acute LC 50 (96 h), as well as final LC 10 values were calculated for the derivation of environmentally safe predicted no effect concentrations (PNEC) for the sediment compartment. PNECs were estimated by both application of assessment factors (AF) and the equilibrium partitioning method (EPM) as proposed by the EU TGD. Finally, environmental risk assessment in a site-specific environment, the Sancti Petri Channel, South Iberian Peninsula, was carried out at three different sampling stations with known environmental LAS concentrations. PNECs obtained by the assessment factor approach with acute toxicity data were one to two orders of magnitude lower than those from the equilibrium partitioning method. On the other hand, when applying lower AFs to the estimated LC 10 values, the PNECs obtained by both approaches were more similar. Environmental risk assessment carried out with the estimated PNECs in a site specific environment with known sediment LAS concentrations revealed that PNECs obtained with acute toxicity data were over conservative whereas those obtained with AF = 10 on LC 10 data and EPM produced more realistic results in accordance with field observations carried out in the study area.

Acute and chronic activity of perchlorate and hexavalent chromium contamination on the survival and development of Culex quinquefasciatus Say (Diptera: Culicidae)

Effects of water contamination with perchlorate and hexavalent chromium [Cr (VI)] on the mosquito Culex quinquefasciatus were assessed. The chronic (10-day) LC 50s values for perchlorate and chromium were 74 ± 8.0 mg/L and 0.41 ± 0.15 mg/L, respectively. Relative Growth Index, a measure of growth and mortality rates in a population, was significantly reduced within 5 days for levels of perchlorate as low as 25 mg/L and for levels of chromium as low as 0.16 mg/L. Neither compound altered wing length of surviving adults. In combination, contaminants were synergistic, causing 14% more mortality than predicted. Acute (24-h) LC 50 values for perchlorate and Cr (VI) were 17,000 ± 3200 and 38 ± 1.3 mg/L, respectively. Effects on mosquito larvae in contaminated environments are likely to be observed for Cr (VI) but not for perchlorate, which generally does not occur at levels as high as those shown here to affect larval mosquitoes.

The Acute and Chronic Toxicity of Hexadecyl and Heptadecyl Sulfate to Aquatic Organisms

HSAS (high-solubility alkyl sulfate) is a new anionic surfactant composed predominantly of methyl and ethyl branched hexadecyl and heptadecyl sulfate. Effects of HSAS on a wide range of fish, algae, and invertebrates were investigated in conventional laboratory toxicity tests as well as in exposures conducted as part of an experimental stream model ecosystem study. For invertebrates and fish, C(16.7)HSAS (average alkyl chain length 16.7) acute LC(50) values ranged from 0.23 (channel catfish) to 2.9 (Asiatic clam, Corbicula) mg/L in well and river waters. LC(50) values for those species tested in both waters were typically within a factor of 1.5 and all were within a factor of 2 of each other, suggesting bioavailability is similar in these waters. Chronic toxicity values ranged from 0.070 (fathead minnow) to 0.42 (amphipod, Hyalella) mg/L across fish and invertebrates with algal chronic toxicity values ranging from 0.5 (blue-green algae, Anabaena flos-aquae) to 7.8 (green algae, Scenedesmus) mg/L. The order of sensitivity to HSAS acute and chronic toxicity was fish = invertebrate > algae. Based on the chronic single species sensitivity distribution, the concentrations protective of 90 and 95% of species were estimated to be 0.058 and 0.036 mg/L, respectively. These compare well with the model ecosystem NOEC of 0.064 mg/L.

Correlation weighting of valence shells in QSAR analysis of toxicity

In the rainbow trout ( Oncorhynchus mykiss), we studied the acute toxicity LC 50-96h of 274 organic pesticides with a wide variety of molecular structures. Optimization of correlation weights of local and global graph invariants (OCWLGI) gave quantitative structure–activity relationships (QSARs) for predicting toxicity. We used a labeled hydrogen-filled graph (LHFG) to elucidate the molecular structure. We also used the extended connectivity of zero ( 0EC k ), first ( 1EC k ), and second ( 2EC k ) order, numbers of path lengths 2 (P2 k ) and 3 (P3 k ) starting from a given vertex in the LHFG, and valence shells of second order (S2 k ). S2 k is the sum of the degree of vertices at distance 2 from a given vertex k. The presence of three-, five-, and six-member cycles and hydrogen bond indices suggested they might be used as global LHFG invariants. We applied this method to a broad set of pesticides, to predict toxicity for the trout. The best model used weighted S2 k and global LHFG invariants. Statistical characteristics of this model are as follows: n = 233, r 2 = 0.7689, r 2(pred) = 0.7688, s = 0.75, F = 769 (training set); n = 41, r 2 = 0.6421, r 2(pred) = 0.4241, s = 1.14, F = 70 (test set).

Toxicity of atrazine to the juvenile hard clam, Mercenaria mercenaria

The herbicide atrazine is one of the most heavily used pesticides in the United States. The effects of atrazine on the clam Mercenaria mercenaria were evaluated in aqueous and sediment laboratory assays. Juvenile clams of approximately 1 mm in size were used for all experiments. An acute aqueous bio-assay was used to determine the 96-h LC 50 for the juvenile clams. A chronic aqueous bioassay was conducted at lower atrazine concentrations over a 10-day exposure period to examine both lethal and sublethal (dry mass, shell size, and condition index) endpoints. A chronic sediment bioassay examined mortality and sublethal endpoints in a 10-day exposure. The acute 96-h LC 50 was 5608 μg/L with 95% confidence intervals ranging from 5003 to 6287 μg/L. Results of the chronic aqueous assay indicated both lethal and sublethal (reduced shell size) effects at high atrazine concentrations. In the 10-day chronic aqueous assay, the no observable effect concentration was 500 μg/L, the lowest observable effect concentration was 1000 μg/L, and the maximum allowable toxicant concentration (MATC) was 707 μg/L. There were no significant effects of atrazine in the chronic sediment exposure. Safe concentrations for the aqueous experiments were estimated by applying an uncertainty factor of 10 to the calculated MATC values. While there were adverse effects of atrazine at high concentrations, these results suggest that atrazine is not directly toxic to M. mercenaria at environmentally relevant concentrations.

Toxicity and hazard assessment of fipronil to Daphnia pulex

Hazard assessments based on two measures of toxicity were conducted for the water flea, Daphnia pulex (Leydig) exposed to the insecticide, fipronil. The measures of toxicity obtained were 48 h acute lethal concentration estimates, and a direct measure of population growth rate, the 10-day instantaneous rate of increase ( r i). Additionally, life tables were developed after exposure to several concentrations to tease out the apparent sublethal effects of this insecticide to D. pulex. The acute LC 50 was estimated to be 0.0156 (0.0088–0.083) mg/L. In the 10-day population growth rate study, extinction of D. pulex populations occurred after exposure to 0.08 mg/L of fipronil, which was equivalent to the 48 h acute LC 75. The NOEC and LOEC for population size after a 10-day exposure to fipronil were 0.03 and 0.05 mg/L, respectively. An expected environmental concentration (EEC) in freshwater lakes/ponds based on an application rate of 250 mg ai/ha (recommended rate for use in Tephritid fruit fly control programs) was estimated to be 0.00017 mg/L. Hazard assessments were developed by dividing the EEC by the LC 50 and NOEC for population size. The assessments based on the LC 50 and NOEC for population size were 0.011 and 0.0057, respectively, indicating that fipronil does not pose a hazard to D. pulex when applied at the rates recommended for control of Tephritid fruit flies. Life tables were developed after exposure to two insecticide concentrations and a control. Exposure to 0.015 mg/L, the approximate 48 h acute LC 50, resulted in only a slight decrease in the net reproductive rate ( R o), birth rate ( b), and intrinsic rate of increase ( r m) and an increase in generation time ( T), death rate ( d), and doubling time (DT) compared to the control. Exposure to 0.03 mg/L, the approximate 48 h acute LC 60, and NOEC in the 10-day study, resulted in a 57% decline in the net reproductive rate, a 1.45-fold decrease in birth rate, a 1.5-fold decrease in the intrinsic rate of increase, a 6-day increase in generation time, a 4-fold increase in death rate, and a 1.5-fold increase in doubling time. The stable age distribution (after 60 days) of D. pulex changed after exposure to fipronil. Increasing concentrations of fipronil resulted in a decrease in the percentage of individuals in the first, second, third, and fourth juvenile stages, an increase in the adult stage, and no change in the adolescent stage. These results indicate that certain concentrations of fipronil approaching the LC 50 can negatively affect population parameters of D. pulex, but that EECs, at least for fruit fly control, should be lower than the concentration necessary to cause damage.

Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite.

Sodium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Potassium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are inorganic salts that function as reducing agents in cosmetic formulations. All except Sodium Metabisulfite also function as hair-waving/straightening agents. In addition, Sodium Sulfite, Potassium Sulfite, Sodium Bisulfite, and Sodium Metabisulfite function as antioxidants. Although Ammonium Sulfite is not in current use, the others are widely used in hair care products. Sulfites that enter mammals via ingestion, inhalation, or injection are metabolized by sulfite oxidase to sulfate. In oral-dose animal toxicity studies, hyperplastic changes in the gastric mucosa were the most common findings at high doses. Ammonium Sulfite aerosol had an acute LC(50) of >400 mg/m(3) in guinea pigs. A single exposure to low concentrations of a Sodium Sulfite fine aerosol produced dose-related changes in the lung capacity parameters of guinea pigs. A 3-day exposure of rats to a Sodium Sulfite fine aerosol produced mild pulmonary edema and irritation of the tracheal epithelium. Severe epithelial changes were observed in dogs exposed for 290 days to 1 mg/m(3) of a Sodium Metabisulfite fine aerosol. These fine aerosols contained fine respirable particle sizes that are not found in cosmetic aerosols or pump sprays. None of the cosmetic product types, however, in which these ingredients are used are aerosolized. Sodium Bisulfite (tested at 38%) and Sodium Metabisulfite (undiluted) were not irritants to rabbits following occlusive exposures. Sodium Metabisulfite (tested at 50%) was irritating to guinea pigs following repeated exposure. In rats, Sodium Sulfite heptahydrate at large doses (up to 3.3 g/kg) produced fetal toxicity but not teratogenicity. Sodium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite were not teratogenic for mice, rats, hamsters, or rabbits at doses up to 160 mg/kg. Generally, Sodium Sulfite, Sodium Metabisulfite, and Potassium Metabisulfite were negative in mutagenicity studies. Sodium Bisulfite produced both positive and negative results. Clinical oral and ocular-exposure studies reported no adverse effects. Sodium Sulfite was not irritating or sensitizing in clinical tests. These ingredients, however, may produce positive reactions in dermatologic patients under patch test. In evaluating the positive genotoxicity data found with Sodium Bisulfite, the equilibrium chemistry of sulfurous acid, sulfur dioxide, bisulfite, sulfite, and metabisulfite was considered. This information, however, suggests that some bisulfite may have been present in genotoxicity tests involving the other ingredients and vice versa. On that basis, the genotoxicity data did not give a clear, consistent picture. In cosmetics, however, the bisulfite form is used at very low concentrations (0.03% to 0.7%) in most products except wave sets. In wave sets, the pH ranges from 8 to 9 where the sulfite form would predominate. Skin penetration would be low due to the highly charged nature of these particles and any sulfite that did penetrate would be converted to sulfate by the enzyme sulfate oxidase. As used in cosmetics, therefore, these ingredients would not present a genotoxicity risk. The Cosmetic Ingredient Review Expert Panel concluded that Sodium Sulfite, Potassium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are safe as used in cosmetic formulations.

Estrogenicity and acute toxicity of selected anilines using a recombinant yeast assay

Suspected estrogen modulators include industrial organic chemicals (i.e., xenoestrogens), and have been shown to consist of alkylphenols, bisphenols, biphenylols, and some hydroxy-substituted polycyclic aromatic hydrocarbons. The most prominent structural feature identified to be important for estrogenic activity is a polar group capable of donating hydrogen bonds (i.e., hydroxyl) on an aromatic system. The present study was undertaken to explore the estrogenic activity and acute toxicity of chemicals containing a weaker hydrogen bond donor group on aromatic systems, i.e., the amino substituent. There is a great deal of chemical similarity between aromatic amines (anilines) and aromatic alcohols (phenols). The chemicals chosen for the current study contained an amino-substituted benzene ring with hydrophobic constituents varying in size and shape. Thus, 37 substituted aromatic amines were assayed for estrogenic activity EC 50 and acute toxicity LC 50 using the Saccharomyces cerevisiae recombinant yeast assay. While the EC 50 of 17-β-estradiol occurs at the 10 −10 range, the aniline with the greatest activity had an EC 50 of 10 −6 M. Thus, anilines, in general, are capable only of very weak estrogenic activity in this assay. A comparison of estrogenic potency between the present group of anilines and a set of previously tested analogous phenols indicated that anilines are consistently less estrogenic than phenols. A comparison of hazard indices (EC 50/LC 50) of these chemicals revealed that, for the vast majority of anilines, the EC 50 and LC 50 were in the same order of magnitude. More specifically, estrogenic activity of para-substituted alkylanilines increases with alkyl group size up to 5 carbons in length, after which the acute toxicity of the larger alkyl-substituents precluded the ability of the compound to induce the estrogenic response.

Histopathological responses of newly hatched larvae of whitefish ( Coregonus lavaretus s.l.) to UV-B induced toxicity of retene

Positively phototactic fish larvae may be exposed to increased ultraviolet-B (UV-B) radiation alone or, potentially and in addition, to polycyclic aromatic hydrocarbons (PAHs) such as retene (7-isopropyl-1-methylphenanthrene) at the egg or larval stages. Suspended and sedimental particulate material near pulp and paper mills may act as sources of retene in chemically contaminated lake areas. In laboratory conditions whitefish larvae were pre-exposed to retene (10, 32 and 100 μg/l), with relevant controls, and irradiated in semi-static tests for 3 h once a day (2 consecutive days) with two UV-B doses (CIE-weighted 2.8 or 5.4 kJ per m 2 per day) or with visible light only. These UV-B doses correspond with slightly subambient and 80% increases relative to the natural maximum daily doses of the solar UV-B in Finland in early May. The UV-B radiation alone increased mortality only slightly (2.7 and 4.0%, respectively). Similarly, no mortality was observed due to retene alone. On the contrary, simultaneous UV-B and retene exposure caused very high mortality to whitefish and all larvae died in the highest retene concentration. The photoinduced acute LC 50 for retene was 13.3 μg/l. Retene treated fish exhibited signs of behavioral irritation and hypoxia during and after the exposure to UV light. Severe skin damages were detected in larvae exposed simultaneously to retene and UV-B. The structural signs of sunburn could also be seen in UV-B and solvent controls (DMSO) with UV-B. Even at the lowest retene concentration, the number of mucous cells increased significantly in simultaneous chemical and UV-B treatment. We consider the tissue reaction as protective response against UV induced retene toxicity. Further, regarding liver parenchyma, fish exposed to retene with UV-B had lesions, revealing hepatotoxicity. We suggest that synergism of the UV-B radiation and the photoactivating pollutants such as retene is a potential risk factor to be taken into consideration in lake areas chemically contaminated by the pulp and paper industry.