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An international panel of experts was engaged to assess the cancer weight of evidence (WOE) for three lower acrylates: methyl acrylate, ethyl acrylate, and 2-ethylhexyl acrylate. The review was structured as a three-round, modified Delphi format, a systematic process for collecting independent and deliberative input from panel members, and it included procedural elements to reduce bias and groupthink. Based upon the available science, the panel concluded: (1) The MOA for point of contact tumors observed in rodent cancer bioassays that is best supported by available data involves increased cell replication by cytotoxicity and regenerative proliferation; (2) The WOE supports a cancer classification of "Not likely to be carcinogenic to humans" a conclusion that is more in line with an IARC classification of Group 3 rather than Group 2 B; (3) Quantitative cancer potency values based on rodent tumor data are not required for these chemicals; and (4) Human health risk assessment for these chemicals should instead rely on non-cancer, precursor endpoints observed at the point of contact (e.g., hyperplasia). The degree of consensus (consensus scores of 0.84-0.91 out of a maximum score of 1) and degree of confidence (7.7-8.7 out of a maximum score of 10) in the WOE conclusions is considered high., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:The project was financed by the Basic Acrylic Monomer Manufacturers (BAMM), Inc., Contract 072,522. The authors listed on the cover page certify that they have no conflict of interest to declare. Authors SMH and CRK are independent consultants and are owners of SciPinion. The paper was subjected to a review for completeness and clarity by members of BAMM and are employed by commercial companies with a financial interest in the subject matter, but were not permitted to revise opinions or conclusions., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The LD50 test was introduced by Trevan in 1927 for biological standardization of dangerous drugs. Since then, the LD50 has gained wide acceptance as a measure of acute toxicity of all types of substances. Recently, however, the LD50 test has been criticized as an unnecessary waste of resources. Therefore, efforts have been made to reduce the number of animals used in such tests and to avoid using this test unless required by regulations. A review of the literature has shown that a relatively small number of animals per dose level (5) and a small number of dose levels (2 or 3) are usually sufficient to calculate an LD50 and slope using moving average methods. In addition, one sex should suffice since large sex differences are seldom encountered. When a formal LD50 is not required, one of several approximate methods may be used to estimate the lethal dose. Future approaches include in vitro cytotoxicity methods and computer-based structure-activity models. The in vitro methods are still in an early stage of development and will require extensive validation before they are accepted by the toxicology community. In conclusion, when LD50 tests are required, the most economical approach should be used, without undue concern for statistical precision.

In general, the carcinogenic potential of petroleum-derived materials is related to the polycyclic aromatic hydrocarbon (PAH) content. Thus it has been assumed that liquids which boil below the PAH distillation range (i.e., below approx. 370 degrees C (700 degrees F) would not be carcinogenic. Several early studies supported this conclusion but were of relatively short duration. Several recent and more rigorous studies have shown that repeated application of certain petroleum-derived materials boiling between approximately 177-370 degrees C (350-700 degrees F) (i.e., middle distillate fuels) can produce tumors in mouse skin. The current studies assessed the tumorigenic potential of a series of middle distillates which varied with respect to boiling range, composition, and source of blending stocks. All of the samples produced evidence of weak tumorigenic activity which was characterized by low tumor yields and long median latencies. However, the majority of the tumor yields were significantly different from the control. There were no apparent differences in response among the samples. Thus the various parameters examined did not substantially influence tumor outcome. In particular, there was no association of tumorigenic activity with aromatic carbon content; this finding, coupled with evidence that PAH levels were low, suggested that the tumorigenic responses were not PAH-dependent. In addition to the tumors, there was evidence of non-neoplastic dermal changes including hyperplasia. These may have contributed to the tumorigenic responses; however, the actual mechanism of tumor induction is unknown.