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Filename: drivers/Session_files_driver.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Backtrace:
File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Filename: helpers/my_audit_helper.php
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Function: str_replace
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Filename: controllers/Detail.php
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Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Filename: controllers/Detail.php
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Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
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Function: require_once
Background: The presence of pharmaceuticals in the environment is a growing global concern and although environmental risk assessment is required for approval of new drugs in Europe and the USA, the adequacy of the current triggers and the effects-based assessments has been questioned.
Objective: To provide a comprehensive analysis of all regulatory compliant aquatic ecotoxicity data and evaluate the current triggers and effects-based environmental assessments to facilitate the development of more efficient approaches for pharmaceuticals toxicity testing.
Methods: Publicly-available regulatory compliant ecotoxicity data for drugs targeting human proteins was compiled together with pharmacological information including drug targets, Cmax and lipophilicity. Possible links between these factors and the ecotoxicity data for effects on, growth, mortality and/or reproduction, were evaluated. The environmental risks were then assessed based on a combined analysis of drug toxicity and predicted environmental concentrations based on European patient consumption data.
Results: For most (88%) of the of 975 approved small molecule drugs targeting human proteins a complete set of regulatory compliant ecotoxicity data in the public domain was lacking, highlighting the need for both intelligent approaches to prioritize legacy human drugs for a tailored environmental risk assessment and a transparent database that captures environmental data. We show that presence/absence of drug-target orthologues are predictive of susceptible species for the more potent drugs. Drugs that target the endocrine system represent the highest potency and greatest risk. However, for most drugs (>80%) with a full set of ecotoxicity data, risk quotients assuming worst-case exposure assessments were below one in all European countries indicating low environmental risks for the endpoints assessed.
Conclusion: We believe that the presented analysis can guide improvements to current testing procedures, and provide valuable approaches for prioritising legacy drugs (i.e. those registered before 2006) for further ecotoxicity testing. For drugs where effects of possible concern (e.g. behaviour) are not captured in regulatory tests, additional mechanistic testing may be required to provide the highest confidence for avoiding environmental impacts.
Download full-text PDF |
Source |
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http://dx.doi.org/10.1016/j.envint.2019.04.075 | DOI Listing |
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