The environmental sustainability of cardboard packaging as well as safety, especially those for food and pharmaceutical products is a recently significant area of research. How to provide usable packaging and protect the environment, product, health and consumer safety, including the best available technologies, closed circular flow, energy and material flow at the same time, is the basis for sustainable development and with in ecological sustainability. That is the reason why researches and development are necessary starting with sustainable graphic design and materials, production, printing on packaging, finishing processes, use and disposal of the product used. The researches carried out in this paper were conceived with the support of experimental design. Samples for research are printed in offset printing. A special printing form is designed that contains the following printing elements: a standard CMYK stapler wedge ranging from 10 % to 100 % RTV values, a color illustration of the packaging product and a standard wedge of 378 fields for ICC profiles. Samples are divided into 18 series depending of the used graphical material. Various combinations of variables are used: cartons (recycled and virgin fibers and FSC fibers and algae from the Adriatic Sea), inks (without mineral oils differing in the proportion of renewable raw materials and inventive combination of resin / oil and mineral oil based inks), varnishes (water-dispersive varnish, UV cured varnish, and non-varnishes prints). The first part of the research: Determining the impact of defined environmental conditions on ΔL *, Δa *, Δb * and ΔE * for the separation of CMYK ink full tone, 70 %, 50 % and 30 % RTV, including all series of measurements. Samples are exposed to the effect of solar radiation through the windows glass at a dynamic of 7, 14, 28, 56 and 112 days during the summer. By using experimental design, statistical models are created and relevant meteorological factors are also taken into account. The second part of the research: Exposure of the imprints to accelerated thermal ageing at air without NO2 presence and with it. The prints are exposed at concentrations of 100 and 800 ppm of NO2 with a dynamics of 1 to 5 days. The colorimetric characteristics of the prints ΔL *, Δa *, Δb * and ΔE * are determined for the separation of CMYK ink, for full tone printing, 70 %, 50 % and 30 % of RTV values. Using statistical methods, the impact of defined variables on the experimental unit property is monitored.The third part of the research refers to the efficiency of reusing of prints and the determination of optical characteristics of handsheets made from recovered fibers including image analysis, brightness and effective resional ink concentration. For statistical data processing a multifactorial analysis of variances is used. The results obtained by measuring the relevant optical parameters have been demonstrated by changes in the use of innovative inks composition including the share and type of renewable raw material combined with cardboard with alternative raw material - green algae from the Adriatic Sea. When evaluating changes in chromatographic characteristics of CMYK color separation prints depending on RTV (100 %, 70 %, 50 % and 30 %), the influence of inks / substrate interaction, dynamic and specificity of exposure to sunlight exposure through window glass and accelerated thermal aging without or with NO2. Laboratory handsheets made of fibers obtained by the recovery of prints by the three-phase method have satisfactory properties, expected from ecologically acceptable paper. Using multivariate analysis, conclusions are drawn in the context of optimization of research processes and new formulations of some graphic materials and are particularly important in the design of environmentally sustainable graphical products.