Integrating process safety with molecular modeling-based risk assessment of chemicals within the REACH regulatory framework: benefits and future challenges.

Registration, evaluation and authorization of chemicals (REACH) represents a recent regulatory initiative by the European union commission to protect human health and the environment from potentially hazardous chemicals. Under REACH, all stakeholders must submit (thermo)physical, thermochemical, and toxicological data for certain chemicals. The commission's impact assessment studies estimate that the costs of REACH will be approximately 3-5 billion Euros. The present study advocates the systematic incorporation of computational chemistry and computer-assisted chemical risk assessment methods into REACH to reduce regulatory compliance costs. Currently powerful computer-aided ab initio techniques can be used to generate predictions of key properties of broad classes of chemicals, without resorting to costly experimentation and potentially hazardous testing. These data could be integrated into a centralized IT decision and compliance support system, and stored in a retrievable, easily communicable manner should new regulatory and/or production requirements necessitate the introduction of different uses of chemicals under different conditions. For illustration purposes, ab initio calculations are performed on heterocyclic nitrogen-containing compounds which currently serve as high energy density materials in the chemical industry. Since investigations of these compounds are still in their infancy, stability studies are imperative regarding their safe handling and storage, as well as registration under REACH.

[1]  Steven M. Bachrach,et al.  The group equivalent reaction: An improved method for determining ring strain energy , 1990 .

[2]  Paola Gramatica,et al.  Introduction General Considerations , 2022 .

[3]  Ilie Fishtik,et al.  Response reactions: A mathematical well-defined way to obtain accurate thermochemistry from ab initio calculations , 2003 .

[4]  M S Mannan,et al.  Prediction of reactive hazards based on molecular structure. , 2003, Journal of hazardous materials.

[5]  Paul von Ragué Schleyer,et al.  Alkyl Substituent effects on the stability of protonated benzene , 1974 .

[6]  S. Hammerum,et al.  Heats of formation and proton affinities by the G3 method , 1999 .

[7]  R. Sivaramakrishnan,et al.  Ring conserved isodesmic reactions: A new method for estimating the heats of formation of aromatics and PAHs. , 2005, The journal of physical chemistry. A.

[8]  John D. Walker,et al.  Use of QSARs in international decision-making frameworks to predict ecologic effects and environmental fate of chemical substances. , 2003, Environmental health perspectives.

[9]  Peter Gray,et al.  Physics And Chemistry Of The Inorganic Azides , 1959 .

[10]  John A. Pople,et al.  Approximate fourth-order perturbation theory of the electron correlation energy , 1978 .

[11]  E. C. Gilbert,et al.  The Heats of Combustion of Some Nitrogen Compounds and the Apparent Energy of the N-N Bond1a,b , 1951 .

[12]  Ivan Gutman,et al.  Response reactions in chemical thermodynamics , 1996 .

[13]  Leo Radom,et al.  Gaussian‐2 (G2) theory: Reduced basis set requirements , 1996 .

[14]  Ilie Fishtik,et al.  Group Additivity vs Ab Initio , 2003 .

[15]  Beth Sirull.  Prepare now for REACH compliance , 2005 .

[16]  Ravindra Datta,et al.  Group Additivity Methods in Terms of Response Reactions , 2003 .

[17]  Pekka Pyykkö,et al.  Relativistic effects in structural chemistry , 1988 .

[18]  David J. Frurip,et al.  Theoretical Methods for Computing Enthalpies of Formation of Gaseous Compounds , 2007 .

[19]  Sanjeev R. Saraf,et al.  Integrating molecular modeling and process safety research , 2004 .

[20]  Leo Radom,et al.  CALCULATION OF PROTON AFFINITIES USING THE G2(MP2,SVP) PROCEDURE , 1995 .

[21]  Leo Radom,et al.  Molecular orbital theory of the electronic structure of organic compounds. IV. Internal rotation in hydrocarbons using a minimal Slater-type basis , 1970 .

[22]  J. Jaworska,et al.  Summary of a workshop on regulatory acceptance of (Q)SARs for human health and environmental endpoints. , 2003, Environmental health perspectives.

[23]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[24]  S. N. Foner,et al.  On the heat of formation of diimide , 1978 .

[25]  Leo Radom,et al.  Molecular orbital theory of the electronic structure of organic compounds. V. Molecular theory of bond separation , 1970 .

[26]  Krishnan Raghavachari,et al.  Gaussian-2 theory using reduced Moller--Plesset orders , 1993 .

[27]  R. A. Back,et al.  The heat of formation of N2H2 and the proton affinity of N2 , 1976 .

[28]  Paul I. Barton,et al.  Computer aided identification of chemical reaction hazards , 1997 .

[29]  Krishnan Raghavachari,et al.  Accurate thermochemistry for larger molecules : gaussian-2 theory with bond separation energies. , 1997 .

[30]  Ken Geiser,et al.  The U.S. Experience in Promoting Sustainable Chemistry (9 pp) , 2005, Environmental science and pollution research international.

[31]  Krishnan Raghavachari,et al.  GAUSSIAN-3 THEORY USING DENSITY FUNCTIONAL GEOMETRIES AND ZERO-POINT ENERGIES , 1999 .

[32]  David Pearce,et al.  Regulatory assessment for chemicals: a rapid appraisal cost–benefit approach , 2004 .

[33]  Lennox E. Iton,et al.  Theoretical and inelastic neutron-scattering studies of tetraethylammonium cation as a molecular sieve template , 1994 .

[34]  L. Curtiss,et al.  Gaussian-3 (G3) theory for molecules containing first and second-row atoms , 1998 .

[35]  John D. Walker,et al.  Use of QSARs in international decision-making frameworks to predict health effects of chemical substances. , 2003, Environmental health perspectives.