Absence of clinical benefit of FDG PET-CT in staging T1 part-solid lung adenocarcinoma.

AIM: To assess the rates of nodal and metastatic disease and change in management when staging part-solid T1 lung adenocarcinomas using integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) in a UK population. MATERIALS AND METHODS: This was a retrospective review of PET-CT examinations performed to stage radiologically suspected T1 part-solid lung adenocarcinoma (n=58) from two different centres. Rates of detection of nodal and metastatic disease, change in management, and final patient outcome were recorded. RESULTS: PET-CT changed the stage in one patient from N0 to N1. It did not change final management in any patient. CONCLUSIONS: In this UK population, PET-CT had minimal additional diagnostic benefit in staging patients with T1 part-solid lung adenocarcinoma. Especially given its cost, the inclusion of PET-CT for this indication in guidelines should be reviewed.

Assessment of lymphedema with lymphoscintigraphy: Can nodal quantification help?

Lymphoscintigraphy with combined qualitative and quantitative analysis is reported to be a more sensitive approach to diagnose lymphedema in comparison with the conventional clinical analysis. Our study seeks to evaluate the diagnostic performance of lower limb lymphoscintigraphy with amalgamation of qualitative and quantitative analysis by measuring the ilio-inguinal nodal uptake. This prospective observational study was comprised of 86 patients (172 limbs) diagnosed with lower limb lymphedema. After a thorough clinical grading of edema, radionuclide lymphoscintigraphy was performed as per a dedicated institutional protocol. Ilio-inguinal nodal quantification of tracer uptake was computed along with the visual study of the scans. Additionally, the corresponding mean nodal uptake percentage for each grade of lymphedema was assessed and a cut off nodal uptake percentage to differentiate between normal and abnormal limbs was defined. Although quantitative analysis with nodal uptake percentage provides objective criteria to diagnose lymphedema, it can only act as an adjunct to qualitative method without replacing it. Finally, standardization of procedure for quantitative lymphoscintigraphy is needed including the potential for combining both rate of clearance of tracer from injection site and nodal uptake for quantification.

Comparison between conventional CT and grayscale inversion CT images in the assessment of the post-operative spinal orthopaedic implants.

AIM: To compare the accuracy of the inverted greyscale CT versus the conventional CT in the assessment of post-operative spinal orthopaedic implants and osseous fusion. METHODS: 50 patients who had CT as part of their routine spinal implant follow up were evaluated for the presence of fusion, fracture and loosening with conventional CT and with greyscale inverted CT images. 3 independent observers assessed the images 2 months apart. Diagnostic performance (sensitivity and specificity) of the conventional and greyscale inversion images relative to the reference standard were calculated. Agreement with the reference standard was assessed using Cohen's kappa for conventional and greyscale inversion images. RESULTS: Correct classifications increased when using the greyscale inverted CT images for each reader compared to conventional CT images (40-46, 39 to 42 and 41 to 44 (out of 50)). Inverted images demonstrated better agreement with the reference standard than conventional grayscale images for assessment of fusion (kappa of 0.588 for inverted CT versus 0.484 for conventional CT) and loosening (kappa 0.386 for inverted versus 0.293 for conventional). Sensitivity was increased for assessment of fusion and loosening. McNemar's test performed for assessment of sensitivity differences showed statistical significance (p = 0.038 for fusion and p = 0.0313 for loosening). CONCLUSION: Greyscale inversion CT is a useful adjunct which has advantages (improved sensitivity and better agreement) over conventional CT imaging in cases of fusion and loosening of metallic implants following spinal instrumentation. We recommend the use of both the greyscale inversion CT images and conventional CT imaging when assessing post-operative spinal orthopaedic implants.

RIFM low-exposure fragrance ingredients safety assessment.

The existing information supports the use of these materials as described in this safety assessment. The 167 materials identified in this assessment were evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Target data, read-across analogs and TTC show that these materials are not expected to be genotoxic. The repeated dose, reproductive, and local respiratory toxicity endpoints were evaluated using the TTC for their respective Cramer Classes (see Fig. 1 below) and the exposure to these materials is below the TTC. The skin sensitization endpoint was completed using the DST for non-reactive and reactive materials (900 µg/cm2 and 64 µg/cm2, respectively); exposures are below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on UV spectra; these materials are not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; the materials were found not to be PBT as per the IFRA Environmental Standards, and their risk quotients, based on their current volume of use in Europe and North America (i.e., PEC/PNEC), are <1.

RIFM fragrance ingredient safety assessment, 3,7-dimethyl-1,3,6-octatriene, CAS registry number 13877-91-3.

The existing information supports the use of this material as described in this safety assessment. 3,7-Dimethyl-1,3,6-octatriene was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from 3,7-dimethyl-1,3,6-octatriene and read-across analog myrcene (ß-myrcene; CAS # 123-35-3) show that 3,7-dimethyl-1,3,6-octatriene is not expected to be genotoxic and provide a calculated margin of exposure (MOE) >100 for the repeated dose toxicity and developmental and reproductive toxicity endpoints. The skin sensitization endpoint was completed using the dermal sensitization threshold (DST) for non-reactive materials (900 µg/cm 2 ); exposure is below the DST. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 3,7-dimethyl-1,3,6- octatriene is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to 3,7-dimethyl-1,3,6-octatriene is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 3,7-dimethyl-1,3,6- octatriene was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental oncentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, p-tolualdehyde, CAS Registry Number 104-87-0.

The existing information supports the use of this material as described in this safety assessment. p-Tolualdehyde was evaluated for genotoxicity, repeated dose toxicity, developmental and reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, and environmental safety. Data from read-across analog benzaldehyde (CAS # 100-52-7) show that p-tolualdehyde is not expected to be genotoxic. Data from read-across analog cuminaldehyde (CAS # 122-03-2) provided p-tolualdehyde a No Expected Sensitization Induction Level (NESIL) of 1100 µg/cm2 for the skin sensitization endpoint. The repeated dose toxicity, developmental and reproductive toxicity, and local respiratory toxicity endpoints were completed using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to p-tolualdehyde is below the TTC (0.03 mg/kg/day, 0.03 mg/kg/day, and 1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoints were evaluated based on data from read-across analog 4-ethylbenzaldehyde (CAS # 4748-78-1); p-tolualdehyde is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; p-tolualdehyde was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, 2-methylpropyl pentanoate, CAS Registry Number 10588-10-0.

The existing information supports the use of this material as described in this safety assessment. 2-Methylpropyl pentanoate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog ethyl 2-methylbutyrate (CAS # 7452-79-1) show that 2-methylpropyl pentanoate is not expected to be genotoxic and provide a calculated margin of exposure (MOE) > 100 for the repeated dose toxicity and reproductive toxicity endpoints. Data from read-across analog isoamyl acetate (CAS # 123-92-2) show that there are no safety concerns for 2-methylpropyl pentanoate for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; 2-methylpropyl pentanoate is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material; exposure is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; 2-methylpropyl pentanoate was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, propyl propionate, CAS Registry Number 106-36-5.

The existing information supports the use of this material as described in this safety assessment. Propyl propionate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that propyl propionate is not genotoxic. Data on propyl propionate provide a calculated margin of exposure (MOE) >100 for the repeated dose toxicity, reproductive toxicity, and local respiratory toxicity endpoints. Data from read-across analog pentyl propionate (CAS # 624-54-4) show that there are no safety concerns for propyl propionate for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; propyl propionate is not expected to be phototoxic/photoallergenic. For the hazard assessment based on the screening data, propyl propionate is not persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards. For the risk assessment, propyl propionate was not able to be risk screened as there were no reported volumes of use for either North America or Europe in the 2015 IFRA Survey.