Environmental Toxicology and Chemistry, Vol. 19, No. 3, pp.

685693, 2000 2000 SETAC Printed in the USA .00 0730-7268/00 $9.00

RATIOS BETWEEN ACUTE AQUATIC TOXICITY AND EFFECTS ON POPULATION GROWTH RATES IN RELATION TO TOXICANT MODE OF ACTION
ERWIN W.M. ROEX,* CORNELIS A.M. VAN GESTEL, ANNEMARIE P. VAN WEZEL, and NICO M. VAN STRAALEN
Department of Ecology and Ecotoxicology, Vrije Universiteit, De Boelelaan 1087, 1081 HV Amsterdam, The Netherlands National Institute for Coastal and Marine Management/RIKZ, P.O. Box 20907, 2500 EX The Hague, The Netherlands ( Received 4 February 1999; Accepted 23 June 1999) AbstractEnvironmental risk assessment of chemicals is mostly based on the results of standardized toxicity tests. To obtain environmental quality criteria, extrapolation factors are used that depend on the amount and quality of available data. These extrapolation factors do not, however, take into account the mode of action of the compound tested or the life history of the test organism. In this study, we analyzed the variability in acute-to-chronic ratios (ACRs) for various chemicals in relation to their mode of action. Chemicals were classied as nonpolar narcotics, polar narcotics, specically acting compounds, and heavy metals. As an acute endpoint, the LC50 was used; as a chronic endpoint, the lowest test concentration at which the natural rate of population increase (r) is affected, or LOEC(r), was used. Data were derived from the on-line literature. Nonpolar narcotic chemicals demonstrate the smallest variation in ACRs, and acute tests can be used to derive chronic endpoints for this class. For the other classes, the variation in ACRs is larger. Fish species especially show a relatively large ACR. For heavy metals, differences in the mode of action may play an important role in explaining differences in ACRs. For the other three classes, however, it is less reliable to predict chronic toxicity using the results of acute tests. In general, differences in species sensitivity rather than in mode of action for the chemical seem to determine differences in ACRs. KeywordsAction mode Acute ratios Chronic ratios Population increase

INTRODUCTION

Many potentially toxic chemicals are present in the environment, and each acts on ecologic targets via their own specic mode of action. Because of time and costs, ecologic risk assessment is mostly based on toxicity data obtained from standardized laboratory tests. Usually, an extrapolation factor is used to derive environmental quality criteria to assure the safety of populations in the eld and, consequently, of the ecosystem itself. Below this safe level, the toxicant should have no adverse effects on the ecosystem. Several approaches can be used to apply these extrapolation factors. In The Netherlands, calculation of a maximum acceptable risk level is often applied. In this approach, the amount of data available determines the extrapolation factor that is used. For the aquatic environment, this means that if at least four no-observed-effect concentrations (NOECs) are available from chronic toxicity tests with species representing different taxa (e.g., sh, crustaceans, algae, or another aquatic taxon), the maximum acceptable risk level is dened as the concentration at which 95% of the species in an ecosystem is protected. If fewer data are available, xed extrapolation factors (e.g., 10, 100, or 1,000) are applied to the lowest available LC50 or NOEC to determine a maximum acceptable risk level [1]. Use of xed application factors implies that the relationship between acute and chronic toxicity is considered to be independent of the test species and test compound. The ratio of acute and chronic effect levels for different species is assumed to be the same, regardless of differences in life histories. In addition, every compound is supposed to have the same acute* To whom correspondence may be addressed (roex@bio.vu.nl). 685

to-chronic ratio (ACR), regardless which life-history attribute is affected by chronic exposure. These assumptions may result in under- or overestimation of the toxicity in the eld when using the xed extrapolation factors. In this study, we investigate the ACR in relation to the mode of action of the toxicant. For organic pollutants, four main mechanisms can be distinguished based on the primary processes that cause toxicity [2]. The rst, nonpolar narcosis, is also called baseline toxicity. This type of action results from rather inert chemicals, which act via a nonspecic mode of action and nally produce an effect that is characterized as narcosis. The severity of this narcosis-type effect and the rate at which the effect occurs depend on the hydrophobicity of the compound. Quantitative structure-activity relationships can be used to predict the toxicity of this class of compounds, examples of which include chlorobenzenes, alcohols, esters, ethers, and chlorinated alkanes. The second main mechanism is polar narcosis. These chemicals also act by narcosis, but they are slightly more toxic than the rst class. Toxicity can not only be explained by hydrophobicity, however, because the capability of these substances to form hydrogen bonds probably also results in enhanced toxicity. Two important groups of chemicals are included in this class of compounds: (substituted) phenols, and (substituted) anilines. The third mechanism is aspecic reactivity. This class consists of electrophile chemicals that react in an aspecic way with nucleophile groups in macromolecules, and these chemicals may exhibit their toxicity through different modes of action. These toxicants have a pronouncedly enhanced toxicity compared with narcosis. Examples include aldehydes and epoxides.

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The fourth mechanism is specic reactivity. This class consists of toxicants with a specic cellular receptor as a target, such as the different classes of pesticides. In addition, however, polychlorinated biphenyls and some polycyclic aromatic hydrocarbon metabolites belong to this class. As a fth independent class, we distinguish the group of heavy metals. This class can have many different modes of action on organisms depending on the properties of the heavy metal itself and on the test species. Because of the already-mentioned time- and cost-consuming aspects of chronic toxicity tests, especially those involving higher organisms such as sh species, several studies have tried to nd quantitative relationships between acute and chronic effect levels, or the so-called ACRs. All these studies have used different approaches, beginning with the studies of McKim [3,4], who reviewed several partial and complete lifecycle tests with sh. He concluded that partial life-cycle tests including sensitive life-cycle stages provide a good estimation of the maximum acceptable toxicant concentration during lifecycle exposure. Kenaga [5] concluded that industrial organic chemicals, which for the most part are narcotics, have smaller ACRs than pesticides and heavy metals, and that ACRs between species were within an order of magnitude from each other. In another study [6], a strong correlation was found between chronic lethality as predicted using acute lethality, and the observed chronic lethality for sh species. For an ecologically important endpoint such as reproduction, however, the correlation failed, probably because a similar mode of action was supposed for acute and chronic exposure. Heger et al. [7] found no satisfying correlation between acute and chronic toxicity, and they concluded that in addition to the substance itself, toxic effects also depend on the test species and the chosen endpoint. Lange et al. [8] concluded that an ACR of 73 would safely predict the NOEC for 90% of the substances. They also concluded that substances such as heavy metals, organometals, and pesticides could yield much higher ACRs. Van der Wal et al. [9] found a strong relationship between the LC50 and a NOEC for growth, thereby resulting in an average ACR of 3.76. They concluded that this relationship was independent of the mode of action for the toxicant. They also concluded that the amount of available data was a limitation in their analysis. In all these studies, the acute effect level was obtained for a standardized exposure period, resulting in 24- or 48-h LC50 values for invertebrates and 96-h LC50 values for vertebrates. Depending on the test organism and the literature available, different chronic tests are used, and these vary from partial life-cycle or early life-stage tests to full life-cycle tests. Several endpoints that differ regarding time of exposure and level of biologic organization are compared. In our opinion, chronic toxicity data for toxicants with different modes of action can only be compared when a standardized parameter, which also has ecologic relevance, is used. In the literature, the parameter that is regarded as being the most relevant ecologically is the intrinsic rate of population increase, or r [10,11]. This population growth parameter is calculated according to the EulerLotka equation [12]:

The parameters in the life table, which determine the life history of an individual (i.e., survival, reproduction, and length of the reproductive period) are translated into one, overall population growth parameter [13]. The aim of this study was to investigate whether the acutechronic extrapolation factors that are used in risk assessment can be supported by toxicity data from the literature. To accomplish this, we compared standardized acute and chronic endpoints for organic toxicants and metals. The classication of Verhaar et al. [2] was used to divide the organic toxicants into different classes. This classication is based on differences in the mode of action between toxicants and, hence, differences in acute toxicity. Vaal et al. [14] showed that differences in species sensitivity may also cause signicant differences in acute toxicity within a class of compounds. How these differences in species sensitivity affect relationships between acute and chronic toxicity, however, is not yet clear. Our study differs from others in this eld in that we used a population growth parameter as a standardized chronic endpoint. Our hypothesis is that a xed relationship exists between the acute and chronic effect concentrations within a class of compounds because of a similar mode of action. Only for the class of chemicals acting via a specic mechanism do we expect to nd a different pattern because of the variety of modes of action. The relationship between acute and chronic toxicity is expressed as the ACR, and the second aim of our study was to investigate differences in ACRs between the different classes of toxicants.
MATERIALS AND METHODS

To investigate our hypothesis, an on-line literature study was performed in which acute and chronic effect levels of compounds belonging to the different classes were reviewed. The LC50 was chosen as an endpoint for acute toxicity tests. The duration of these tests is typically 24 or 48 h for invertebrates and 96 h for vertebrates. As a chronic endpoint, the LOEC(r) was chosen. This parameter is dened as the lowest observed effect concentration at which the intrinsic rate of population increase (r) is affected. Only experiments in which r was calculated as a chronic endpoint were considered. If r was not calculated but sufcient life-table data were given, then r was approximated according to

ln(Re)/Te

lx mx e

rx

(1)

where lx is the fraction of survival of a population counted from birth till age x and mx is the number of offspring per individual of age x per unit of time. These parameters can be calculated when performing life-table response experiments.

where Re represents the reproductive rate, which is the mean number of offspring produced per individual at the end of the experiment, and Te represents the duration of the experiment. Two different procedures were used to determine the LOEC(r). If statistical tests were used, the lowest concentration 0.05 is retested that was different from the control at p garded as the LOEC(r). If no statistical methods were used, the LOEC(r) was considered to be the concentration at which r was reduced by at least 20%. In this case, four or more concentrations must be tested, thus resulting in a distinct concentration-effect relationship. Toxicants must be applied via the water phase. If the values of test concentrations were doubtful, water-solubility values were checked using the ClogP software (MedChem, Claremont, CA, USA) [15]. Experiments in which test concentrations exceeded the water solubility were excluded from the data set. As a consequence, only life-cycle studies in which the test organisms were exposed to the test compound for at least one life cycle (i.e., from egg to reproductive stage) were included.

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Fig. 1. Log LOEC(r) versus log LC50 for nonpolar narcotics.

Fig. 3. Log LOEC(r) versus log LC50 for compounds acting via a specic mechanism. Black dots represent data points excluded from the regression analysis.

RESULTS

To exclude differences in circumstances between acute and chronic experiments, only studies from which both a LC50 and a LOEC(r) could be calculated on the basis of the same experiment were used. Concentrations ( M) were scaled on a log-log basis because of the wide range of both acute and chronic toxicity values. Linear regression by a least-squares approximation was used to establish a relationship between the LOEC(r) and the LC50 according to equation log LOEC(r)

a log LC50

where the y-intercept, or b, represents the logarithm of the ACR. If the slope of the regression, or a, is close to one, then the ACR is constant. For other values of the slope, however, the ACR is concentration dependent. The SYSTAT 5.2.1 software package (Systat, Evanston, IL, USA) was used to determine signicant differences between y-intercepts and slopes of regressions for the different chemical classes. For this purpose, we calculated the slope of a data set for two of the classes of compounds. A likelihood ratio test was used to compare these results with those obtained in the case of each class having its own slope parameter. The same method was used to compare y-intercepts.

Most of the studies in our data set used aquatic invertebrates, because these test organisms are easy to breed, have a relatively short life cycle, and can be followed during their complete life cycle. Moreover, most of these species are parthenogenetic, which makes it easier to perform reproduction studies. An overview of the toxicity data that proved to be useful for our study is given in the Appendix. Figures 1 to 4 show regression curves for the several modes of action. Data were scarce for the class of reactive compounds, however, and no relationship could be established. For the other chemical classes, sufcient data were available to develop a relationship between the acute and chronic toxicity endpoints. Figure 1 shows the relationship between the log LOEC(r) and the log LC50 for substances acting by nonpolar narcosis. The species tested were the cladocerans Daphnia magna and Ceriodaphnia dubia [1618] and the rotifer Brachionus calyciorus [19]. Regression resulted in a correlation coefcient of 0.928 and a slope of 0.916. This indicates that the ACR within this class is constant. Figure 2 presents the results for chemicals acting by polar narcosis. Test species for which suitable data were found included the cladocerans Daphnia magna and Ceriodaphnia

Fig. 2. Log LOEC(r) versus log LC50 for polar narcotics. Black dots represent data points excluded from the regression analysis.

Fig. 4. Log LOEC(r) versus log LC50 for heavy metals. The black dot represents the data point excluded from the regression analysis.

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Table 1. Characteristics of regression lines for different classes of compoundsa

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Class Nonpolar narcotics Polar narcotics Specic acting Metals

a b

y-Intercept
0.237A 0.426AB 0.943B 0.587

Slope 0.916A 0.820A 0.985A 0.725

n
11 12 45 34 0.05.

Average ACRb 2.58 9.8 17.31 15.31 1.57A 11.8B 26.6AB 28.8

Values followed by the same uppercase letter within a column are not signicantly different at p ACR acute-to-chronic ratio.

quadrangula [2023], the polychaete Ophryotrocha diadema [24], the sh species Brachydanio rerio [25] and Poecilia reticulata [26], and the rotifers Brachionus rubens [27] and B. calyciorus [19,28,29]. The data set of compounds consisted of substituted and unsubstituted anilines and phenols. Two groups of data could be distinguished: a large group (represented in Fig. 2 by open dots), and a smaller group (represented in Fig. 2 by closed dots). Regression analysis was only performed for the large group. The small group, which had a larger ACR, was composed of the data for Ceriodaphnia quadrangula, Poecilia reticulata, and Ophryotrocha diadema exposed to 3,4-dichloroaniline and of the data for Brachydanio rerio exposed to 4-chloroaniline [2326]. Without these data, the correlation is high (R2 0.845), and the slope of the curve is 0.820. The data on which regression analysis was performed (open dots in Fig. 2) also included tests with organisms exposed to 3,4-dichloroaniline and 4-chloroaniline. This indicates that after chronic exposure, differences in species sensitivity are more important than differences in toxicant sensitivity. Figure 3 shows the results for compounds acting via a specic mode of action. The compounds involved were neurotoxic chlorinated pesticides and synthetic pyrethroids, cholinesterase-inhibiting carbamates and organophosphates, uncouplers of oxidation, an insect growth regulator, a herbicide, and a fungicide. Data were found for seven species of cladocerans, two species of copepods, two species of rotifers, a mysid, a polychaete worm, and the sh species fathead minnow (Pimephales promelas) and bluegill sunsh (Lepomis macrochirus) [19,2756]. This class covers a broad range of LC50 values, varying from 0.69 nM for the very toxic, synthetic pyrethroid fenvalerate to 5.9 mM for the relatively nontoxic compound tetramethylthioureum. Despite the acute modes of action for this group of substances being heterogeneous, a good relationship between the LOEC(r) and the LC50 was found, with a regression coefcient of 0.904. This relationship is constant over a wide range of acute toxicities, as indicated by the slope of the curve (0.985). The ACR of the fathead minnow exposed to the organophosphate esters azinphos-methyl and chlorpyrifos [51,52] was larger than that for the rest of the data, and these two data points were excluded from the regression analysis. Figure 4 shows the results for heavy metals on nine species of cladocerans [5769], a copepod [70], a rotifer [19], a mysid shrimp [71], and the sh species Pimephales promelas [72] and Poecilia reticulata [73]. The variation in ACRs was larger than that for the other chemical classes. Consequently, no good relationship could be established between the acute and chronic endpoints. Despite the great variation in ACRs within this class, however, the ACR of the guppy exposed to zinc was clearly larger than that for the rest of the data set, and this data point was omitted from the regression analysis.

The average ACR of the total data set, which included all classes of compounds considered but without the deviating 24.92. values, was 14.38 Table 1 summarizes the characteristics of the regression equations for the different classes of chemicals. The results for the heavy metals are not considered here, however, because of the poor correlation within this group. Some signicant differences were found, but the relationship between the acute and chronic toxicity endpoints, as chosen in this study, was of the same size for all classes of chemicals. The average ACR for polar narcotics, however, appears to be signicantly higher than the average ACR for nonpolar narcotics.
DISCUSSION AND CONCLUSIONS

When comparing ACRs derived in this study with values found in the literature, two points should be kept in mind. First, we used LOECs instead of NOECs, because this increased our data set. Second, we used population growth rate as the chronic parameter. The small average ACR found within the class of nonpolar narcotics (2.58 1.57) is as expected because of the aspecic mode of action for these compounds. The mode of action remains the same on chronic exposure, which means that the effects measured in chronic studies represent a smaller magnitude of the same kind of response (i.e., a LOEC for survival instead of a LC50). If another mode of action became active, the ACR would probably increase [74]. The average ACR for nonpolar narcotics as found in our study is small compared with those in other studies. From the data reported by Richter 4.62 for nonpolar naret al. [75], an average ACR of 6.43 cotics could be calculated based on an LOEC for reproduction by Daphnia magna. In that study, chronic mortality was not taken into account. From a study by Kuhn et al. [76], an ACR 46.5 could be calculated based on a 21-d NOEC of 40.8 test for Daphnia magna. In most cases, reproduction was the most sensitive parameter, except for toluene, for which mortality was the most sensitive. From a study by Cowgill and 434 could be extrapolated. Milazzo [77], an ACR of 237 The chronic toxicity endpoint in that study was the NOEC based on a three-brood test for two species of daphnids. The large standard deviation was caused by ethanol, for which the ACRs were several orders of magnitude higher. Without these data, however, the ACR was in the range found during the 0.69). Cowgill and Milazzo [77] study (i.e., 2.37 Potential differences in species sensitivity in our study could not become clear because of the lack of variation among test species in our data set. In our data set, acute toxicity tests provide a good estimate of the chronic toxicity endpoint, LOEC(r). In most of the chronic experiments within this group, mortality was the rst population parameter to be affected. For these kinds of substances and test species, the prediction method of Mayer et al. [6] would work well.

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The average ACR for the class of polar narcotics was signicantly higher than that for the class of nonpolar narcotics. Because of the diversity of test organisms, it becomes apparent that differences in species sensitivity exist when different species are exposed to the same toxicant. Some anilines are rapidly metabolized by some sh species [78,79], and the formed metabolites may cause other effects in long-term tests. This implies that the result of a standardized acute test with a certain species cannot be extrapolated to chronic effects in other species. The outcome probably depends largely on the metabolic capacities and life history of the test species. From the study of Cowgill and Milazzo [77], an ACR of 2.74 could be calculated for polar narcotics, which is 7.66 in the same range as that found in this study. In the study by Kuhn et al. [76], which used Daphnia magna as a test species, a distinction could be made in ACRs between two groups: the (chlorinated) phenols, with a small average ACR (23.9 33.5); and the (chlorinated) anilines, with a large average ACR (322 418). Based on these ndings, Urrestarazu Ramos [80] concluded that on chronic exposure, daphnids are more sensitive than other aquatic species to (chlorinated) anilines. This is in contrast with the results of our study, in which daphnids appeared to belong to the least sensitive group of organisms regarding chronic exposure to chlorinated anilines. These differences in outcome most probably are the result of different chronic endpoints being used in these studies. The class of specically acting chemicals has a larger average ACR than the two former groups. This difference is not signicant, however, because of the variation in ACRs within this group. Still, this variation is smaller than that for the ACRs mentioned in the literature [5,7,8]. The diversity in modes of action within this class is large, as expressed by the large range of acute toxicity, but the correlation between chronic and acute endpoints is high. Despite the substantial differences in species sensitivity within acute toxicity tests regarding this class of compounds [14], the diversity in species sensitivity for ACRs is not as pronounced. The poor correlation within the class of heavy metals makes it impossible to compare these compounds with other chemical classes. The same diversity in ACRs within the class of metals was also found by Lange et al. [8]. Differences in properties between essential metals (e.g., copper and zinc) and nonessential metals (e.g., nickel, cadmium, and lead) produce this diversity in ACRs. Though r is a biologically relevant parameter, it also has drawbacks to its use. The complexity and duration of the experiments that are needed to establish the effects of a compound on the natural rate of increase in a population restrict the number of species that can be used. In most experiments, these are organisms that have a short life cycle, are easy to breed, and are parthenogenetic. In general, these organisms do not properly represent the composition of the ecosystem in the eld and, consequently, the effects that a compound will have on the total ecosystem. Establishing the effects on r for a small group of organisms can result in under- or overestimation for a compound in the eld. This may be true for our data set as well. Data that were excluded from the regression analysis because of deviating values, for the most part, consisted of toxicity data involving higher organisms (mostly sh). The diversity in species within our data set is limited, but it seems that differences in species sensitivity rather than in mode of action determine ACRs. Compared with their acute toxicity values, vertebrates seem to be more sensitive than invertebrates

on chronic exposure. As stated earlier, processes such as the bioactivation of certain compounds in sh may play a critical role. This deviating relationship for vertebrates (i.e., sh) between acute and chronic toxicity was also found by Nagel [81]. He performed and evaluated life-cycle tests with sh in which very low chronic effect values could be determined. The duration of an acute toxicity test for sh (i.e., 96 h) seems to be too short to determine an LC50 that can properly predict chronic toxicity. Generally, sh species have a lifetime several magnitudes longer than that of an average aquatic invertebrate, whereas the duration of an acute test is only twice as long. In addition, processes such as uptake and distribution of a toxicant elapse more slowly in larger organisms; therefore, equilibrium between the internal and the external concentration of a compound may not be achieved within 96 h. An external concentration needed to produce 50% mortality in such a short period of time would produce an overestimation of the real LC50. To conclude, acute studies with invertebrates generally provide a good indication of the effects at the population level, but in this group of organisms, large differences in ACRs may exist, even between related species [23]. The average ACR calculated in our study (6.03 3.97) is in good agreement with the extrapolation factors that are used in risk assessment, namely, a factor of 10 between the LC50 and the NOEC [1]. Predicting chronic toxicity levels from the results of acute toxicity tests in sh species seems to be unreliable. Because of the scarcity of ACRs for sh in our study, a good estimate for the reliability of the extrapolation factors currently used in risk assessment is not possible. In our opinion, performance of complete life-cycle tests, despite their time- and cost-consuming aspects, is the only way to estimate the real chronic toxicity of chemicals to sh.
AcknowledgementThis study received nancial support from the Dutch Ministry of Transport, Public Works and Water Management, National Institute for Coastal and Marine Management
REFERENCES 1. Okkerman PC, Van der Plassche EJ, Slooff W, Van Leeuwen CJ, Canton H. 1991. Ecotoxicological effects assessment: A comparison of several extrapolation procedures. Ecotoxicol Environ Safety 21:182193. 2. Verhaar HJM, Van Leeuwen CJ, Hermens JLM. 1992. Classifying environmental pollutants. Chemosphere 25:471491. 3. McKim JM. 1977. Evaluation of tests with early life stages of sh for predicting long-term toxicity. J Fish Res Board Can 34: 11481154. 4. McKim JM. 1985. Early life stage toxicity tests. In Rand GM, ed, Fundamentals of Aquatic Toxicology, 2nd ed. Taylor & Francis, Bristol, UK, pp 9741011. 5. Kenaga EE. 1982. Predictability of chronic toxicity from acute toxicity of chemicals in sh and aquatic invertebrates. Environ Toxicol Chem 1:347358. 6. Mayer FL, Krause GF, Buckler DR, Ellersieck MR, Lee G. 1994. Predicting chronic lethality of chemicals to shes from acute toxicity test data: concepts and linear regression analysis. Environ Toxicol Chem 13:671678. 7. Heger W, Jung S-J, Martin S, Peter H. 1995. Acute and prolonged toxicity to aquatic organisms of new and existing chemicals and pesticides. Chemosphere 31:27072726. 8. Lange R, Hutchinson TH, Scholz N, Solbe J. 1998. Analysis of the ECETOC aquatic toxicity (EAT) database. IIComparison of acute and chronic ratios for various aquatic organisms and chemical substances. Chemosphere 36:115127. 9. Van der Wal JT, Vaal MA, Hoekstra JA, Hermens JLM. 1995. Ordering chemical compounds by their chronic toxicity to aquatic

690

Environ. Toxicol. Chem. 19, 2000

species. A principal component analysis. RIVM Report 719102041. RIVM, Bilthoven, The Netherlands. Van Straalen NM, Kammenga JE. 1998. Assessment of ecotoxicity at the population level using demographic parameters. In Schuurman G, Markert B, eds, Ecotoxicology. John Wiley & Sons. Chichester, UK, pp 621644. Calow P, Sibly RM, Forbes V. 1997. Risk assessment on the basis of simplied life-history scenarios. Environ Toxicol Chem 16: 19831989. Lotka J. 1913. A natural population norm. J Washington Acad Sci 3:241248. Caswell H. 1996. Demography meets ecotoxicology: Untangling the population level effects of toxic substances. In Newman MC, Jagoe CH, eds, Ecotoxicology, A Hierarchical Treatment. Lewis, Chelsea, MI, USA, pp 255292. Vaal M, Van der Wal JT, Hoekstra J, Hermens J. 1997. Variation in the sensitivity of aquatic species in relation to the classication of environmental pollutants. Chemosphere 35:13111327. Biobyte. 1994. ClogP for Windows. Version 1.0.0. MedChem, Claremont, CA, USA. Calamari D, Galassi S, Setti F, Vighi M. 1983. Toxicity of selected chlorobenzenes to aquatic organisms. Chemosphere 12:253262. Gersich FM, Bartlett EA, Murphy PG, Milazzo DP. 1989. Chronic toxicity of biphenyl to Daphnia magna Straus. Bull Environ Contam Toxicol 43:355362. Niederlehner BR, Cairns J Jr, Smith EP. 1998. Modeling acute and chronic toxicity of nonpolar narcotic chemicals and mixtures to Ceriodaphnia dubia. Ecotoxicol Environ Saf 39:136146. Snell TW, Moffat BD. 1992. A 2-d life cycle test with the rotifer Brachionus calyciorus. Environ Toxicol Chem 11:12491257. Francis PC, Grothe DW, Scheuring JC. 1986. Chronic toxicity of 4-nitrophenol to Daphnia magna Straus under static-renewal and ow-through conditions. Bull Environ Contam Toxicol 36:730 737. Gersich FM, Milazo DP. 1988. Chronic toxicity of aniline and 2,4-dichlorophenol to Daphnia magna Straus. Bull Environ Contam Toxicol 40:17. Baird DJ, Barber I, Calow P. 1990. Clonal variation in general responses of Daphnia magna Straus to toxic stress. I. Chronic life-history effects. Funct Ecol 4:399407. Kluttgen B, Kuntz N, Ratte HT. 1996. Combined effects of 3,4 dichloroaniline and food concentration on life-table data of two related cladocerans, Daphnia magna and Ceriodaphnia quadrangula. Chemosphere 32:20152028. Hooftman RN, Vink GJ. 1980. The determination of toxic effects of pollutants with the marine polychaete worm Ophryotrocha diadema. Ecotoxicol Environ Saf 4:252262. Bresch H, Beck H, Eehlermann D, Schlaszus H, Urbanek M. 1990. A long-term toxicity test comprising reproduction and growth of zebra sh with 4-chloroaniline. Arch Environ Contam Toxicol 19:419427. Schafers C, Nagel R. 1991. Effects of 3,4-dichloroaniline on sh populations. Comparison between r- and K-strategists: A complete life cycle test with the guppy (Poecilia reticulata). Arch Environ Contam Toxicol 21:297302. Halbach U, Siebert M, Westermayer M, Wissel C. 1983. Population ecology of rotifers as a bioassay tool for ecotoxicological tests in aquatic environments. Ecotoxicol Environ Saf 7:484513. Ferrando MD, Janssen CR, Andreu E, Persoone G. 1993. Ecotoxicological studies with the freshwater rotifer Brachionus calyciorus. II. An assessment of the chronic toxicity of lindane and 3,4-dichloroaniline using life tables. Hydrobiologia 255256: 3340. Ferrando MD, Andreu-Moliner E. 1991. Acute lethal toxicity of some pesticides to Brachionus calyciorus and Brachionus plicatilis. Bull Environ Contam Toxicol 47:479484. Van Leeuwen CJ, Maas-Diepeveen JL, Niebeek G, Vergouw WHA, Grifoen PS, Van Luijken MW. 1985. Aquatic toxicological aspects of dithiocarbamates and related compounds. I. Shortterm toxicity tests. Aquat Toxicol 7:145164. Van Leeuwen CJ, Moberts F, Niebeek G. 1985. Aquatic toxicological aspects of dithiocarbamates and related compounds. II. Effects on survival, reproduction and growth of Daphnia magna. Aquat Toxicol 7:165175. Green AS, Chandler GT. 1996. Life-table evaluation of sedimentassociated chlorpyrifos chronic toxicity to the benthic Copepod,

E.W.M. Roex et al.

10.

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11. 12. 13.

34. 35.

36. 37. 38. 39.

14. 15. 16. 17. 18. 19. 20.

40. 41. 42.

21.

43.

22.

44. 45.

23.

24.

46. 47. 48. 49.

25.

26.

27.

28.

50. 51. 52.

29.

30.

53.

31.

54. 55.

32.

Amphiascus tenuiremis. Arch Environ Contam Toxicol 31:77 83. Fernandez-Casalderrey A, Ferrando MD, Andreu-Moliner E. 1991. Demographic parameters of Brachionus calyciorus Pallas (Rotifera) exposed to sublethal endosulfan concentrations. Hydrobiologia 226:103110. Fernandez-Casalderrey A, Ferrando MD, Andreu-Moliner E. 1993. Effects of endosulfan on survival, growth and reproduction of Daphnia magna. Comp Biochem Physiol C106:437441. Sunderam RIM, Thompson GB, Chapman JC, Cheng DMH. 1994. Acute and chronic toxicity of endosulfan to two Australian cladocerans and their applicability in deriving water quality criteria. Arch Environ Contam Toxicol 27:541545. Ferrando MD, Sancho E, Andreu-Moliner E. 1995. Effects of lindane on Daphnia magna during chronic exposure. J Environ Sci Health B30:815825. Daniels RE, Allan JD. 1981. Life table evaluation of chronic exposure to a pesticide. Can J Fish Aquat Sci 38:485494. Day K, Kaushik NK. 1987. An assessment of the chronic toxicity of the synthetic pyrethroid, fenvalerate, to Daphnia galeata mendotae, using life tables. Environ Pollut 44:1326. Day NK, Kaushik NK. 1987. Short-term exposure of zooplankton to the synthetic pyrethroid fenvalerate, and its effects on rates of ltration and assimilation of the alga, Chlamydomonas reinhardii. Arch Environ Contam Toxicol 16:423432. McKee J, Knowles CO. 1986. Effects of Fenvalerate on biochemical parameters, survival, and reproduction of Daphnia magna. Ecotoxicol Environ Saf 12:7084. Fairchild JF, Little EE, Huckins JN. 1992. Aquatic hazard assessment of the organophosphate insecticide fonofos. Arch Environ Contam Toxicol 22:375379. Chu KH, Wong CK, Chiu KC. 1997. Effects of the insect growth regulator (S)-methoprene on survival and reproduction of the freshwater cladoceran Moina macrocopa. Environ Pollut 96:173 178. Buhl KJ, Hammilton SJ, Schmulbach JC. 1993. Chronic toxicity of the bromoxynil formulation Buctril to Daphnia magna exposed continuously and intermittently. Arch Environ Contam Toxicol 25:152159. Buhl KJ, Hammilton SJ, Schmulbach JC. 1993. Acute toxicity of the herbicide bromoxynil to Daphnia magna. Environ Toxicol Chem 12:14551468. Ferrando MD, Sancho E, Andreu-Moliner E. 1996. Chronic toxicity of fenitrothion to an algae (Nannochloris oculata), a rotifer (Brachionus calyciorus), and the cladoceran (Daphnia magna). Ecotoxicol Environ Saf 35:112120. Allan JD, Daniels RE. 1982. Life table evaluation of chronic exposure of Eurytemora afnis (Copepoda) to Kepone . Mar Biol 66:179 184. Stephenson GL, Kaushik NK, Solomon KR. 1991. Acute toxicity of pure pentachlorophenol and a technical formulation to three species of Daphnia. Arch Environ Contam Toxicol 20:7380. Stephenson GL, Kaushik NK, Solomon KR. 1991. Chronic toxicity of a pure and technical grade pentachlorophenol to Daphnia magna. Arch Environ Contam Toxicol 21:388394. Morton MG, Mayer FL Jr, Dickson KL, Waller WT, Moore JC. 1997. Acute and chronic toxicity of azinphos-methyl to two estuarine species, Mysidopsis bahia and Cypriniodon variegatus. Arch Environ Contam Toxicol 32:436441. Carlson AR. 1971. Effects of long-term exposure to carbaryl (Sevin) on survival, growth, and reproduction of the fathead minnow (Pimephales promelas). J Fish Res Board Can 29:583587. Adelman IR, Smith LL Jr, Siesennop GD. 1976. Chronic toxicity of Guthion to the fathead minnow (Pimephales promelas Rafinesque). Bull Environ Contam Toxicol 15:726733. Jarvinen AW, Nordling BR, Henry ME. 1983. Chronic toxicity of Dursban (Chlorpyrifos) to the fathead minnow (Pimephales promelas) and the resultant acetylcholinesterase inhibition. Ecotoxicol Environ Saf 7:423434. Van Dam RA, Barry MJ, Ahokas JT, Holdway DA. 1996. Comparative acute and chronic toxicity of diethylenetriamine pentaacetic acid (DTPA) and ferric-complexed DTPA to Daphnia carinata. Arch Environ Contam Toxicol 31:433443. Gersich FM, Mendoza CG, Hopkins DL, Bodner KM. 1984. Acute and chronic toxicity of triclopyrtriethylamine salt to Daphnia magna Straus. Bull Environ Contam Toxicol 32:497502. Fernandez-Casalderrey A, Ferrando MD, Andreu-Moliner E.

Toxicity in relation to mode of action 1992. Effect of sublethal diazinon concentrations on the demographic parameters of Brachionus calyciorus Pallas (Rotifera). Bull Environ Contam Toxicol 48:202208. Fernandez-Casalderrey A, Ferrando MD, Andreu-Moliner E. 1993. Chronic toxicity of methylparathion to the rotifer Brachionus calyciorus fed on Nannochloris oculata and Chlorella pyrenoidosa. Hydrobiologia 255/256:4149. Koivisto S, Ketola M, Walls M. 1992. Comparison of ve cladoceran species in short- and long-term copper exposure. Hydrobiologia 248:125136. Winner RW, Farrell MP. 1976. Acute and chronic toxicity of copper to four species of Daphnia. J Fish Res Board Can 33: 16851691. Winner RW, Keeling T, Yeager R, Farrell MP. 1977. Effect of food type on the acute and chronic toxicity of copper to Daphnia magna. Freshwater Biol 7:343349. Wong CK. 1992. Effects of chromium, copper, nickel, and zinc on survival and feeding of the cladoceran Moina macrocopa. Bull Environ Contam Toxicol 49:593599. Wong CK. 1993. Effects of chromium, copper, nickel, and zinc on longevity and reproduction of the cladoceran Moina macrocopa. Bull Environ Contam Toxicol 50:633639. Wong CK, Wong PK. 1990. Life table evaluation of the effects of cadmium exposure on the freshwater cladoceran, Moina macrocopa. Bull Environ Contam Toxicol 44:135141. Hatakeyama S, Yasuno M. 1981. Effects of cadmium on the periodicity of parturition and brood size of Moina macrocopa (Cladocera). Environ Pollut 26:111120. Bertram PE, Hart BA. 1979. Longevity and reproduction of Daphnia pulex (de Geer) exposed to cadmium-contaminated food or water. Environ Pollut 19:295305. Chandini T. 1989. Survival, growth and reproduction of Daphnia carinata (Crustaceae; Cladocera) exposed to chronic cadmium stress at different food (Chlorella) levels. Environ Pollut 60:29 45. Enserink L, Luttmer W, Maas-Diepeveen H. 1993. Reproductive strategy of Daphnia magna affects the sensitivity of its progeny in acute toxicity tests. Aquat Toxicol 17:1525. Enserink L, De la Haye M, Maas H. 1993. Reproductive strategy of Daphnia magna: Implication for chronic toxicity tests. Aquat Toxicol 25:111124. Bodar CWM, Van Leeuwen CJ, Voogt PA, Zandee DI. 1988.

Environ. Toxicol. Chem. 19, 2000

691

69. 70. 71. 72. 73. 74. 75.

56.

57. 58. 59. 60. 61. 62. 63. 64. 65.

76. 77. 78. 79.

66. 67.

80. 81.

68.

Effect of cadmium on the reproduction strategy of Daphnia magna. Aquat Toxicol 12:301310. Ingersoll CG, Dwyer FJ, May TW. 1990. Toxicity of inorganic and organic selenium to Daphnia magna (Cladocera) and Chironomus riparius (Diptera). Environ Toxicol Chem 9:11711181. Bechman RK. 1994. Use of life tables and LC50 tests to evaluate chronic and acute toxicity effects of copper on the marine copepod Tisbe furcata (Baird). Environ Toxicol Chem 13:15091517. Gentile JH, Gentile SM, Hairston NG Jr, Sullivan BK. 1982. The use of life tables for evaluating the chronic toxicity of pollutants to Mysidopsis bahia. Hydrobiologia 93:179187. Mount DI. 1968. Chronic toxicity of copper to fathead minnows (Pimephales promelas, Ranesque). Water Res 2:215223. Uviovo EJ, Beatty DD. 1979. Effects of chronic exposure to zinc on reproduction in the guppy (Poecilia reticulata). Bull Environ Contam Toxicol 23:650657. Rand GM, Wells PG, McCarty LS.1995. Introduction to aquatic toxicology. In Rand GM, ed, Fundamentals of Aquatic Toxicology, 2nd ed. Taylor & Francis, Bristol, UK, pp 367. Richter JE, Peterson SF, Kleiner CF. 1983. Acute and chronic toxicity of some chlorinated benzenes, chlorinated ethanes and tetrachloroethylene to Daphnia magna. Arch Environ Contam Toxicol 12:679684. Kuhn R, Pattard M, Pernak K-D, Winter A. 1989. Results of the harmful effects of water pollutants to Daphnia magna in the 21 day reproduction test. Water Res 23:501510. Cowgill UM, Milazzo DP. 1991. The sensitivity of Ceriodaphnia dubia and Daphnia magna to seven chemicals utilizing the threebrood test. Arch Environ Contam Toxicol 20:211217. Zok S, Gorge G, Kalsch W, Nagel R. 1991. Bioconcentration, metabolism and toxicity of substituted anilines in the zebrash (Brachydanio rerio). Sci Total Environ 109/110:411421. Bradbury SP, Dady JM, Fitzsimmons PN, Voit MM, Hammermeister DE, Erickson RJ. 1993. Toxicokinetics and metabolism of aniline and 4-chloroaniline in medaka (Oryzias latipes). Toxicol Appl Pharmacol 118:205214. Urrestarazu Ramos E. 1998. Aquatic toxicity of polar narcotic pollutants. PhD thesis. University of Utrecht, Utrecht, The Netherlands. Nagel R. 1994. Complete life cycle tests with zebrashA critical assessment of the results. In Muller R, Lloyd R, eds, Sublethal and Chronic Effects of Pollutants on Freshwater Fish. Blackwell, Oxford, UK, pp 188195.

692

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APPENDIX Toxicity data for the compounds and species used in regression plots

E.W.M. Roex et al.

Compound Nonpolar Chlorobenzene 1,2-Dichlorobenzene 1,4-Dichlorobenzene 1,2,3-Trichlorobenzene 1,2,4-Trichlorobenzene Biphenyl Xylene Trichloroethylene Toluene Ethylbenzene Tetrachloroethylene Polar Trinitrotoluene Phenol Dimethylphenol 4-Nitrophenol 2,4-Dichlorophenol Aniline 4-Chloroaniline 3,4-Dichloroaniline

Species

log LC50 ( M)

log LOEC(r) ( M)

ACRa

Study

Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Brachionus calyciorus Ceriodaphnia dubia Ceriodaphnia dubia Ceriodaphnia dubia Ceriodaphnia dubia Brachionus calyciorus Brachionus rubens Brachionus calyciorus Brachionus calyciorus Daphnia magna Brachionus rubens Daphnia magna Daphnia magna Brachionus rubens Brachydanio rerio Daphnia magna Ceriodaphnia quadrangula Daphnia magna Brachionus calyciorus Ophryotrocha diadema Poecilia reticulata Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Daphnia magna Amphiascus tenuiremis Brachionus calyciorus Pimephales promelas Brachionus calyciorus Daphnia magna Ceriodaphnia dubia Moinodaphnia macleayi Brachionus calyciorus Daphnia magna Daphnia pulex Eurytemora afnis Daphnia galeata Daphnia magna Daphnia magna Moina macrocopa Daphnia magna Daphnia magna Brachionus calyciorus Nannochloris oculata Eurytemora afnis Ophryotrocha diadema Brachionus rubens Brachionus calyciorus Daphnia magna

1.58 0.72 1.04 0.29 0.82 0.37 3.37 2.11 1.61 1.48 1.18 1.60 3.81 3.92 3.23 2.27 1.66 1.20 0.26 2.89 2.56 0.70 1.39 0.14 2.58 1.97 1.73 0.23 0.58 0.55 0.08 0.24 0.34 0.67 0.06 1.14 3.77 0.49 0.14 0.39 0.20 0.71 1.53 0.46 1.10 0.18 0.08 0.28 1.89 0.75 0.18 1.22 3.16 2.22 1.96 0.04 0.56 3.63 1.37 1.62 1.09 0.65 0.22 0.65 0.98

1.43 0.43 0.74 0.26 0.27 0.32 2.58 1.95 1.48 1.20 0.60 1.34 2.33 2.66 1.55 1.86 1.16 0.96 0.30 2.79 0.50 0.31 1.21 0.81 1.49 1.21 1.91 0.66 0.41 1.18 0.49 1.44 1.49 1.36 1.38 0.18 1.63 1.08 1.52 1.22 1.81 1.85 0.03 3.46 0.91 0.53 0.71 1.01 1.71 0.07 0.28 1.88 3.92 3.22 3.49 1.79 0.84 4.42 0.75 1.24 1.69 1.38 0.12 0.15 0.27

1.41 1.95 2.00 3.55 3.55 1.12 6.17 1.45 1.35 1.91 3.80 1.82 29.5 18.2 35.5 2.57 3.16 1.74 3.63 1.26 1,148 10.2 407 8.91 1.09 1,513 4,365 7.76 9.77 53.7 3.71 47.9 14.1 4.90 20.9 9.12 138 37.15 24.0 6.76 40.74 13.8 36.3 1,000 1.55 5.13 6.17 6.76 1.51 6.76 1.26 4.57 5.75 10.0 33.9 67.6 1.91 7.76 4.17 2.40 3.98 107 0.79 6.31 5.13

[16] [16] [16] [16] [16] [17] [19] [18] [18] [18] [18] [19] [27] [19] [19] [20] [27] [21] [21] [27] [25] [23] [23] [22] [28,29] [24] [26] [30,31] [30,31] [30,31] [30,31] [30,31] [30,31] [30,31] [30,31] [30,31] [30,31] [30,31] [30,31] [30,31] [30,31] [32] [19] [52] [33] [34] [35] [35] [28,29] [36] [37] [37] [38,39] [40] [41] [42] [43,44] [45] [45] [45] [46] [24] [27] [19] [47,48]

Specic mechanism Nabam Maneb Zineb DIDTb NaDMDC Ziram Ferbam Thiram TMTMb TMTUb NaDeDC ZnDEDC Disulfuram T(n)PTD Chlorpyrifos Endosulfan

Lindane Dieldrin Fenvalerate Fonofos Methoprene Bromoxynil Fenitrothion Chlordecone Pentachlorphenol

Toxicity in relation to mode of action APPENDIX Continued Compound Aziophos-methyl Carbaryl DTPAb Triclopyr Diazinon 2,4-D Methylparathion Heavy metals Copper Species log LC50 ( M) 2.86 0.78 1.65 2.35 3.66 1.98 2.01 2.80 2.04 0.11 1.23 0.92 0.93 0.13 0.13 0.05 0.03 0.12 0.15 1.36 0.87 0.38 0.05 0.60 0.26 0.54 0.42 0.73 1.06 1.52 1.76 1.15 0.88 1.49 1.87 0.94 2.60 0.37 1.59 1.16 1.4 2.20

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log LOEC(r) ( M) 4.02 2.80 0.53 0.96 2.76 1.21 1.63 2.65 0.88 0.30 1.42 1.22 1.22 0.03 0.10 0.03 0.03 0.03 0.8 2.10 0.28 0.32 1.35 2.15 1.35 0.35 1.21 1.05 0.14 0.64 2.05 0.97 0.41 1.03 1.87 0.31 0.63 0.49 0.70 0.83 1.00 1.79

ACRa 14.5 3,801 13.2 24.5 7.94 5.89 2.40 1.41 14.5 1.55 1.55 2.00 2.34 1.45 1.07 1.2 1.15 1.41 8.91 5.50 14.1 0.87 20.0 35.5 12.3 7.76 42.7 60.3 15.8 7.6 1.95 132 19.5 2.88 5,495 17.8 93.3 7.24 7.76 2.14 2.51 2.57

Study [49] [51] [50] [53] [54] [55] [19] [19] [56] [57] [57] [57] [57] [57] [58] [58] [58] [59] [60,61] [70] [72] [19] [62] [63] [64] [65] [66,67] [68] [19] [69] [71] [71] [71] [60,61] [73] [71] [60,61] [71] [71] [60,61] [66,67] [19]

Mysidophis bahia Pimephales promelas Pimephales promelas Daphnia carinata Daphnia magna Brachionus calyciorus Brachionus calyciorus Brachionus calyciorus Brachionus calyciorus Daphnia magna Bosmina longirostris Chydorus sphaericus Daphnia galeata Daphnia pulex Daphnia magna Daphnia parvula Daphnia ambigua Daphnia magna Moina macrocopa Tishe furcata Pimephales promelas Brachionus calyciorus Moina macrocopa Moina macrocopa Daphnia pulex Daphnia carinata Daphnia magna Daphnia magna Brachionus calyciorus Daphnia magna Mysidopsis bahia Mysidopsis bahia Mysidopsis bahia Moina macrocopa Poecilia reticulata Mysidopsis bahia Moina macrocopa Mysidopsis bahia Mysidopsis bahia Moina macrocopa Daphnia magna Brachionus calyciorus

Cadmium

Selenium Mercury Lead Zinc Nickel Silver Chromium

a b

ACR acute-to-chronic ratio. DIDT 5,6-dihydro-imidazo(2,1-c)-1,2,4-dithiazole-3-thion; TMTM diethylenetriamine pentaacetic acid.

tetramethylthiurammonosulde; TMTU

tetramethylthiourea; DTPA