ACUTE TO CHRONIC RATIO

The acute to chronic ratio (ACR) uses acute toxicity data to gauge the chronic

toxicity (MATC) of a chemical of interest to an organism. The science behind
determining a safe concentration to the environment is imperfect, statistically
limited, and resource intensive. There is an unfilled demand for the rapid
assessment of different chemical toxicity to many different organisms. The ACR
is a proposed solution to this demand.

While empirical methods are crucial to making scientific conclusions and

informed decisions, best personal judgement is often the best tool to the
regulator in allowing or prohibiting potentially toxic chemicals from entering the
environment. This means taking into consideration information about chemical
structure, physical and chemical properties including fate and transport in the
environment, and most importantly toxicological data.[1]

The ACR is mathematically the inverse of the application factor (AF), which was
first proposed by Mount and Stephan (1967).[2] It provides no new information, it
simply converts AF values into whole integer numbers that are more easily
comparable for researchers visually.

Calculation[edit]

The ACR is the inverse of the application factor (AF). This makes it easier for
regulators to visualize data as whole numbers rather than decimals. The AF is
calculated by dividing the Maximum Acceptable Toxicant Concentration (MATC)
by the Lethal Concentration that kills 50% of test organisms in an acute toxicity
test (LC50).

The Maximum Allowable Toxicity Concentration (MATC) is determined by taking

the square root of the No Effects Concentration (NOEC) multiplied by the Low
effect concentration (LOEC).

The Application Factor (AF) is determined by dividing the MATC by the LC50

The ACR is then the inverse of the AF.

Regulatory use[edit]
There are thousands of new and different chemicals that are designed and
synthesized by private chemical manufacturers every year. The public demands
that all of these chemicals go through testing and be approved for use by
the EPA under the TSCA. Part of that testing requirement is determining the
toxicity of chemicals to organisms in the environment.[3]

Law[edit]

Section 5 of the TSCA states that the EPA must respond to pre-manufacturing
notices (PMN) 90 –180 days after submission by the manufacturer. The EPA is
responsible for identifying the substance, its proposed use, amount made,
byproducts, exposure levels, and all existing environmental and health data
necessary to prevent significant harm to the environment.[4] Additionally there
are no PMN test requirements so there is often a minimal amount of data
presented. This may be discussed as a fault of the TSCA.[5] New chemical
PMNs are submitted early in the chemical's development so they rarely contain
information about chronic toxicity - yet the EPA must respond within the 90-180
day time period after submission of the PMN. This essentially puts a huge
burden on the EPA because chemical effects to the environment are extremely
hard to predict simply based on single species toxicity tests (SST).[6] The limited
time period that the TSCA gives the EPA for making this decision requires the
EPA to make decisions with a high amount of uncertainty. This ultimately makes
the goal of protecting the environment from significant adverse effects difficult.

The results of acute and chronic toxicity testing form the basis of knowledge
that regulators draw from in performing work related to ecological risk
assessment and designing policy that defines how much of a chemical of
interest should be allowed in certain environments. While this sounds simple
enough to the layperson, it is extremely difficult in practice due to a large
number of modifying factors inextricably tied to toxicity tests and statistical
analysis.[7] Different toxic effects can be observed from the same chemical
through different types of environmental exposures and parameters, and thus
toxicity results from acute and chronic tests must be jointly considered in
decision making. Additionally, chronic toxicity tests tend to require significantly
more attention and resources than acute tests which makes them much less
feasible for basing decisions off of in a timely manner. The need for
development of more advanced statistical methods, and uniformity in using
these methods by regulators has been made apparent in literature.[8]

Scientific methods for determining acute and chronic toxicity to organisms are
inherently imperfect and non-uniform throughout the field of research, and the
most useful tool for decision making by officials is more often than not best
personal judgement.[9]

A popular new method for ecological risk assessment is the acute to chronic

estimation (ACE). This method uses computer software to estimate chronic
toxicity, which provides similar information with much less effort and expense to
the researcher.

Limitations[edit]

The ACR is derived from data generated by SSTs, as so falls victim to the same
errors and limitations. These limitations are described in detail in literature [10]

Using point estimates such as NOECs/LOECs reduces a data set containing

many values down to an isometric, removing the rich visual information that
allows the researcher to assess the reliability and variability in the data.
Information such as the slope of the dose-response curve, from which NOECs
are LOECs are derived, is lost.[11] However, without NOECs and LOECs
regulatory decisions are much harder to make. While ACR has drawbacks due
to the uncertainty of the point estimates it uses to define it, it is still widely
valued as a regulatory tool in making environmental assessments and policy
decisions.

ACRs are based on tests with a number of different methodologies, which

means that there can be significant variance among ACRs.

References[edit]

1. ^ May, M.; Drost, W.; Germer, S.; Juffernholz, T.; Hahn, S.

(2016). "Evaluation of acute-to-chronic ratios of fish and Daphnia
to predict acceptable no-effect levels". Environmental Sciences
Europe. 28 (1): 16. doi:10.1186/s12302-016-0084-
7. PMC 5044967. PMID 27752449.
2. ^ Mount, D. I.; C. E. Stephan (1967). "A method for establishing
acceptable toxicant limits for fish malathion and the butoxyethanol
ester of 2,4-D". Trans. Am. Fish. Soc. 96 (2):
185. doi:10.1577/1548-8659(1967)96[185:AMFEAT]2.0.CO;2.
3. ^ "Actions under TSCA Section 5 - US EPA". Epa.gov. 2014-10-
24. Retrieved 7 January 2018.
4. ^ Kenaga, E. E. (1982). "Predictability of chronic toxicity from
acute toxicity of chemicals in fish and aquatic
invertebrates". Environmental Toxicology and Chemistry. 1 (4):
347–358. doi:10.1002/etc.5620010410.
5. ^ Office, U.S. Government Accountability (2 December
2009). "Chemical Regulation: Observations on Improving the
Toxic Substances Control Act". Gao.gov (GAO-10-292T).
Retrieved 7 January 2018.
6. ^ Maltby, L.; Clayton, S. A.; Yu, H.; McLoughlin, N.; Wood, R. M.;
Yin, D. (2000). "Using single-species toxicity tests, community-
level responses, and toxicity identification evaluations to
investigate effluent impacts". Environmental Toxicology and
Chemistry. 19: 151–
157. doi:10.1002/etc.5620190118. S2CID 84557436.
7. ^ "ENVIRONMETRICS
AUSTRALIA" (PDF). Environmetrics.net.au. Retrieved 7
January 2018.
8. ^ Fox, D. R.; Landis, W. G. (2016). "Don't be fooled—A no-
observed-effect concentration is no substitute for a poor
concentration–response experiment". Environ Toxicol
Chem. 35 (9): 2141–
2148. doi:10.1002/etc.3459. PMID 27089534.
9. ^ "About Risk Assessment - US EPA". Epa.gov. 2013-12-03.
Retrieved 7 January 2018.
10. ^ Cairns, J. Environ Monit Assess (1984) 4:
259. doi:10.1007/BF00394145
11. ^ Landis, W. G.; Chapman, P. M. (2011). "Well past time to stop
using NOELs and LOELs". Integr Environ Assess Manag. 7 (4):
vi–viii. doi:10.1002/ieam.249. PMID 21932339.