Acetaminophen as an oral toxicant for invasive California kingsnakes (Lampropeltis californiae) on Gran Canaria, Canary Islands, Spain

Invasive species are threatening biodiversity and ecosystem stability globally. The introduction of the California kingsnake (Lampropeltis californiae) on Gran Canaria, Canary Islands, Spain represents an emerging invasion that is already threatening endemic island species. Dead neonatal mice treated with 80-mg acetaminophen tablets are approved as a registered pesticide for control of invasive brown treesnakes (Boiga irregularis) in Guam and could potentially be used as an oral toxicant to control invasive California kingsnake populations. We sought to evaluate oral toxicity of acetaminophen and to determine the dosage necessary for lethal control of invasive California kingsnake populations. Dead mice inserted with a known acetaminophen dose (0 mg, 40 mg, 60 mg, and 80 mg) were fed to California kingsnakes from Gran Canaria. Each dose was tested in 20 male and 20 female snakes representing the size range found in Gran Canaria. After snakes ate their dead mouse, they were monitored for mortality, regurgitation, and time of death and regurgitation. Treatments of 60 mg and 80 mg had 100% mortality, while 40 mg had 87.5% mortality. No control snakes died. Time to death occurred on average 38.6 hours after consuming the dead mouse. The top two time to death models accounted for 97% of model weights and included variables dosage (mg/kg), sex, and dosage * sex or those terms plus body condition index. Out of the 116 snakes that died, 97 regurgitated the mouse that contained the acetaminophen capsule, and time to regurgitation was highly correlated with time to death. Acetaminophen is a highly effective oral toxicant for California kingsnakes. Dead mouse baits treated with acetaminophen have potential as a control method on Gran Canaria but should not solely be expected to protect native species or eradicate California kingsnakes on Gran Canaria. Future efforts should focus on preventing California kingsnakes from invading other Canary Islands.


Introduction
Many reptiles have successfully invaded ecosystems outside of their natural range (Kraus 2009). For example, the Balearic Islands have more invasive than native reptiles (Pinya and Carretero 2011). Invasive reptiles are often generalist (wide diet breadth and climate tolerance), which aids them in invading ecosystems with environmental conditions that overlap with those of their native ranges (Filz et al. 2018). When reptiles are introduced intentionally (e.g. releasing unwanted pets) or accidently (e.g. stowaways in cargo) into novel ecosystems, they can have negative impacts on native species. For instance, the brown anole (Anolis sagrei Duméril and Bibron, 1837) has successfully invaded the southeastern United States from the Bahamas and displaced the native green anole (Anolis carolinensis Cuvier and Voigt, 1832) to fringe habitat throughout much of its range (Stuart et al. 2014), and the invasive common house gecko (Hemidactylus frenatus Schlegel, 1836) has outcompeted native species, such as the mourning gecko (Lepidodactylus lugubris Duméril and Bibron, 1836), across the Pacific basin for food resources (Petren and Case 1996).
Invasive snake populations are threatening biodiversity of island and mainland ecosystems because snakes are effective predators (Campbell et al. 2012). Reducing an invasive snake population's threat towards native species is challenging because snakes are difficult to locate and remove due to their cryptic nature. International trade and human movement have established multiple invasive snake populations. Transporting ornamental plants, primarily olive trees, is thought to be a main vector of recent establishment of invasive horseshoe whip snake (Hemorrhois hippocrepis Linnaeus, 1758), montpellier snake (Malpolon monspessulanus Hermann, 1804), and ladder snake (Rhinechis scalaris Schinz, 1822) populations in the Balearic Islands (Silva-Rocha et al. 2015). The introduction of the wolf snake (Lycodon aulicus Linnaeus, 1758) in Christmas Island, Australia (Fritts 1993) and Mauritius (Tonge 1990) and the brown treesnake (Boiga irregularis Bechstein, 1802) in Guam  are also thought to be due to snakes becoming stowaways in ships' cargo. Other invasive snake populations have been aided by the exotic pet trade. Pet snakes being released or escaping captivity have established invasive populations of Burmese pythons (Python molurus Linnaeus, 1758) and boa constrictors (Boa constrictor Linnaeus, 1758) in southern Florida (Snow et al. 2007;Dorcas et al. 2012) and corn snakes (Elaphe guttata Linnaeus, 1766) and boa constrictors in multiple Caribbean islands (Perry et al. 2003;Bushar et al. 2015).
Invasive snake populations can potentially have large cascading effects on ecosystems they invade. The invasion of the Burmese python into southern Florida has resulted in the dramatic decline of the medium-sized mammal community (Dorcas et al. 2012 (Dorcas et al. 2012). One of the largest ecological and economic catastrophes due to a reptilian invasive species is the invasion of the brown treesnake on Guam, which resulted in the loss of native birds (Savidge 1987;Wiles et al. 2003), mammals (Rodda et al. 1997), and lizards Campbell et al. 2012) through overconsumption. The collapse of Guam's native avifauna has resulted in an ecosystem cascade affecting other taxa, such as arthropod distribution and abundance (Rogers et al. 2012) and loss of ecosystem services such as seed dispersal (Rogers et al. 2017).
An emerging snake invasion is occurring on Gran Canaria, Canary Islands, Spain, with the introduction of the California kingsnake (Lampropeltis californiae Blainville, 1835), a medium-sized constricting colubrid. The California kingsnake is a generalist predator that is widely distributed in western and southwestern United States and northwestern Mexico (Markel 1989;Stebbins 1998). Since 1998, California kingsnakes have been found outside of captivity on Gran Canaria and been considered officially established in 2007 (Pether and Mateo 2007). California kingsnakes were introduced to Gran Canaria through the pet trade, and either escaped or were released from captivity into an ecosystem with no natural predators. Currently there are established California kingsnake populations in Telde-Valsequillo, Gáldar, and Maspalomas in Gran Canaria (Fisher et al. 2019). The established populations are genetically distinct, indicating that they are from different founder groups (Monzón-Argüello et al. 2015).
There are no native snake species on Gran Canaria, so California kingsnakes represent a novel threat to prey species. In areas of Gran Canaria inhabited by California kingsnakes, endemic lizard populations are at risk, including Gran Canaria skink (Chalcides sexlineatus Steindachner, 1891) and Gran Canaria giant lizard (Gallotia stehlini Schenkel, 1901) due to California kingsnake predation (Cabrera-Pérez et al. 2012;Monzón-Argüello et al. 2015). Size distribution of Gran Canaria giant lizard populations have shifted towards primarily larger adults that are too big for California kingsnakes to consume (Gallo-Barneto R, GESPLAN, unpublished). The decreasing Gran Canaria giant lizard population could impact local vegetation because Gran Canaria giant lizards are frugivores and potentially important seed dispersers like the closely related Gallotia galloti Oudart, 1839 on nearby Tenerife (Valido et al. 2003).
Gran Canaria has contracted Gestión y Planeamiento Territorial y Medioambiental S.A. (GESPLAN), a private organization, to manage LIFE+ Lampropeltis, a California kingsnake capture and public outreach program. LIFE+ Lampropeltis has utilized active searching, funnel traps, coverboard traps, and a public call response program to attempt to capture California kingsnakes to achieve their primary goal of reduction and eventual eradication of California kingsnake populations on Gran Canaria. LIFE+ Lampropeltis's capture methods have not been able to stop California kingsnake's continual range expansion. Gran Canaria California kingsnakes have greater average clutch size (Cabrera-Pérez et al. 2012) and body mass index (Fisher et al. 2019) compared to California kingsnakes in their native range. Due to ample food resources and minimal predation, California kingsnakes have been able to rapidly increase population size and have the potential to continue to do so. Additional methods are needed to prevent further California kingsnake spread on Gran Canaria and increased endangerment of endemic species.
Following the invasion of Guam by accidentally-introduced brown treesnakes, and the subsequent ecological and economic impacts (Savidge 1987;Wiles et al. 2003;Rodda and Savidge 2007), acetaminophen (known internationally as paracetamol) was identified as a safe, humane, and effective toxicant for brown treesnake control (Savarie et al. 2000;Johnston et al. 2002). Acetaminophen mouse baits-80-mg tablets coupled with a dead newborn mouse (DNM) bait, the most effective brown treesnake bait matrix tested to date (Savarie and Clark 2006)-have become an integral part of brown treesnake interdiction and control programs on Guam (Clark et al. 2018) and are registered for use as a brown treesnake pesticide with the US Environmental Protection Agency . Hand-placing of acetaminophen mouse baits in bait stations can be more cost-effective than trapping ) and has demonstrated the ability to greatly reduce brown treesnake abundance on a landscape scale (Savarie et al. 2001). Acetaminophen mouse baits have also been adapted and proven effective for aerial bait applications over inaccessible forest habitats Dorr et al. 2016) and are currently being manufactured for distribution via an automated aerial delivery system for landscape-scale control of brown treesnakes . The first small-scale aerial eradication attempt has commenced in an experimental forest plot surrounded by a snake exclosure fence (SRS, unpublished).
Subsequent to demonstrating effectiveness for brown treesnake control, acetaminophen has been tested as a tool for lethal control of other invasive reptiles and been found effective for juvenile Burmese pythons (Mauldin and Savarie 2010), juvenile Nile monitors (Varanus niloticus Hasselquist, 1762; Mauldin and Savarie 2010), and Jackson's chameleons (Trioceros jacksonii Boulenger, 1896; Van Kleeck and Holland 2018). Results were less promising for black spiny-tailed iguana (Ctenosaura similis Gray, 1831; Avery et al. 2011), at least at low dosages. These results have not yet translated to any significant management actions for invasive reptile control.
Lethal control of wildlife is always controversial and invokes concerns about humaneness of methods to be employed. The proximate mode of action causing death by acetaminophen toxicity in brown treesnakes is methemoglobinemia, wherein elevated levels of methemoglobin interfere with blood cells' ability to bind or release oxygen resulting in anemic hypoxia (Mathies and Mauldin 2020). Methemoglobinemia is considered a relatively humane mode of action with low severity and short duration of symptoms (Ruell et al. 2019), similar to CO 2 immersion which is considered to be a humane means of euthanasia (AVMA 2013).
Although acetaminophen has been evaluated as a humane and effective toxicant for other invasive reptiles, any recommendations for application in a management scenario should be preceded by confirmation of its efficacy for the target species. Given the potential dire consequences of the California kingsnake invasion of the Canary Islands, we sought to evaluate oral toxicity of acetaminophen and to determine the dosage necessary for lethal control of invasive California kingsnake populations.

Study animals
We obtained a total of 132 California kingsnakes from Gran Canaria for this study. All snakes we used for the study were either captured with funnel or coverboard traps or active searches in Telde-Valsequillo and Gáldar by LIFE+ Lampropeltis. LIFE+ Lampropeltis shipped all snakes to O' Hare International Airport, Chicago in May 2017, where we transported the snakes to their housing facilities at Truman State University in Magruder Hall room 3434, Kirksville, Missouri. For each snake, we determined sex by cloacal probing (Reed and Tucker 2012), measured mass (0.1 g) by placing a snake into a tared container on an electronic balance, and measured snout-vent length (SVL; 0.1 cm) by gently stretching the snake's body along a flexible cloth measuring tape. We assigned each snake a unique individual identification number. We then housed 1 to 5 snakes together based on similar size and same sex in plastic containers (57.9 × 42.4 × 17.8 cm or 34.6 × 21 × 12.4 cm) with newspaper substrate, a hide box, outside label with snake identification number(s), and water ad libitum. Group-housed snakes were separated for feedings to prevent competition. We checked snakes daily to ensure cages were clean and had enough water. We allowed snakes to acclimate for three months at a room temperature of 25 °C before trials began. After the acclimation period, we fed snakes a dead feeder mouse each month until they were tested (Truman State University raised mice equivalent to ~ 10% of the snake's body mass).

Body condition index
We derived a snake body condition index (CI) as the residuals from a quadratic linear regression of log(mass) and log(SVL) and scaled to a standard normal distribution so that values are in units of standard deviations from the mean of zero (e.g., Siers et al. 2017 PLOSONE). Snakes with positive CI values are heavier than predicted by length and are presumed to have greater energy stores (Bonnet and Naulleau 1995). . Red and blue boxes are mean ± 1 standard deviation for females and males, respectively. The dark vertical line is the mean of both sexes, and the dark horizontal line is ± 1 standard deviation of both sexes. Statistical tests for differences among all pairwise comparisons of treatment groups indicated no substantial length or mass biases.

Test group assignment and treatments
We assigned snakes to treatment groups that would receive acetaminophen doses of 0, 40, 60, and 80 mg [model term DOSE] and derived the massspecific dosage [DOSAGE] as mg of acetaminophen per kg of snake mass (mg/kg). We assigned snakes to dose-specific treatment groups with equal sex ratios and such that distributions of size and mass would not be biased among groups. We verified that there were no biases in length and mass with an ANOVA and confirmed no pairwise differences among test groups with a Tukey's HSD test. There were no marked length or mass differences in pairwise comparisons among treatment groups (Tukey-adjusted p = 0.097-0.990 [SVL] and 0.334-1.000 [mass]). See Figure 1 for comparison of length and mass distributions.
We prepared acetaminophen treatments by filling gelatin capsules with measured doses of powdered acetaminophen (CAS#103-90-2, Sigma-Aldrich, St. Louis). We implanted capsules into dead feeder mice (3.1-10.0 g) via abdominal incisions; mice for the 0-mg control group were implanted with empty capsules. At the beginning of the trial we offered each snake a treated mouse, which was either voluntarily ingested or we coerced the snake to feed by inserting the mouse into the snake's oral cavity.
Our initial treatment group sizes were N = 40, 35, 29, and 28, respectively. After establishing 100% survival in the 0-mg negative control group, we re-used 29 of the control snakes in the treatment groups to maximize the amount of data that could be obtained with the limited number of animals available for trials. Re-used snakes were selected to balance sex and mass among treatment groups. After we reassigned control group snakes to the 40, 60, and 80-mg treatment groups, our sample sizes were N = 20:20, 20:20, 20:20, and 20:21 (F:M), respectively. In order to control against potential artefacts of re-use of control snakes, we assigned a data covariate to identify individuals that were re-used [CONTROL]. We later evaluated whether re-use of these individuals had any influence on mortality or time until death; if the term carried no explanatory value, we removed it from the model.
We fed snakes between the hours of 1000 and 1400 and checked snakes every 2 hours between 7 a.m. and 11 p.m. until they had died or survived for more than 7 days. We recorded whether the snake had regurgitated its treatment mouse [REGURG], and recorded time to death [TTD] and time to regurgitation [TTR] as the midpoint between successive observations when death or regurgitation were noted (hours). We also noted general observations of snake behavior during the trials. All animal procedures were reviewed and approved by the Truman State University Institutional Animal Care and Use Committee (IACUC) per Protocol #17-7.

Statistical methods
Factors affecting efficacy (percent mortality) would be properly evaluated with a logistic regression, with effect size assessed in the model output. However, as we will report in Results, our data did not have enough variability to be properly modeled. Rather, we estimated and plotted means and 95% binomial compatibility intervals (exact method) and tested all pairwise comparisons among treatment groups using the R function "pairwise.prop.test" (Holm method) for p-value adjustments for multiple comparisons.
For snakes that died, we evaluated factors influencing time to death using Cox proportional hazard models as implemented in the R package "survival" (https://github.com/therneau/survival). Because dosage in relation to mass (mg/kg) is derived from dose and mass, and dosage is the more direct measure of the mechanics of toxicity, we elected to only consider models including the term DOSAGE rather than terms for dose and mass. We also considered the influence of terms for sex [SEX], an interaction of sex and dosage [SEX*DOSAGE], body condition index [CI], whether the snake regurgitated [REGURG], and whether the snake had previously been used in the control group [CONTROL]. We log-transformed and scaled all continuous predictor variables for modeling to improve normality of distribution and model convergence [SVL, MASS, CI, DOSAGE]. We evaluated models with all combinations of these terms in an Aikake's Information Criterion (AIC) model selection framework (e.g., Burnham and Anderson 2002) adjusted for small sample size (AIC c ). We considered the summed weights of models containing respective terms as an index of relative variable importance (RVI; Anderson 2008). Per convention, we considered models with a ΔAIC c of −2 or less to be superior models, and models within ΔAICc of −2 of the top model to be plausible alternative models. As a check against uninformative parameters (Arnold 2010)which increase AICc by ~ 2 units over the same model without that term while adding nothing to the model fit as evaluated by adjusted R 2 -we also verified compatibility of the data with respective hypotheses based on p-values from z-distributions.
We evaluated the relationship between time to regurgitation and time to death with a linear regression model. Because they were tightly correlated, we do not report Cox proportional hazard models for time to regurgitation; preliminary exploratory modelling showed nearly identical results to time to death models. For each dosed individual that regurgitated and died, we calculated the proportional relationship between times to regurgitation and death (time to regurgitation*time to death -1 ).
All statistical tests were performed in R version 3.6.0 (R Core Team 2019). In addition to AIC c values, p-values from statistical tests are evaluated for compatibility of the data with the respective hypothesis without assignment of an arbitrary threshold of significance or non-significance, and 95% compatibility intervals are assessed for the point estimates (sensu Amrhein et al. 2019).

Results
Acetaminophen dosing was highly efficacious, with 100% mortality in the 60 and 80-mg treatment groups, and 87.5% mortality (5/40 surviving) in the 40-mg treatment group. In pairwise comparisons of mortality rates, the control group, with zero mortalities, was clearly different than any of the treatment groups (p << 0.001). The p-value for the difference between the 40 mg treatment group and the 60 or 80 mg groups (0.121) was marginally compatible with a hypothesis of lower efficacy (Figure 2). When evaluated by sex, results were the same with no differences between males and females within treatment group, and all treated groups differed from the control group (p << 0.001).
The dosages we evaluated ranged from 75.3 to 2230 mg/kg (Figure 3). The highest dosage that a snake survived in this study was 401 mg/kg; this appears to be an outlier because all 71 snake dosages in between the highest and second highest survival dosage (133 mg/kg) died (Figure 3). Including this extreme value, our data set would indicate that the LD 100 (dosage above which all snakes died) is 401 mg/kg, with an LD 99 (dosage above which 99% of snakes died) of > 133 mg/kg. The lowest lethal dosage (LDLo) in this study was 94.2 mg/kg. Because our tests were so efficacious, we did not get enough survival data across a range of lower dosages in order to calculate

Time to death
Time to death ranged from 14 to 80 hours after ingestion of acetaminophen-treated mice, with a mean of 38.6 hours (SD ± 13.2). All models comprising the top 99% of total model weights included the terms DOSAGE, SEX, and DOSAGE*SEX as predictors of time to death. The model containing only these terms outcompeted the top model that did not include all three by ΔAIC c = −10.92, and the top model that included none of them by −31.52. Other models within the top 99% of summed model weights included these terms along with one or more of the remaining terms of CI, REGURG, and CONTROL. However, in the models containing DOSAGE+SEX+DOSAGE*SEX plus just one of these terms, p-values for REGURG and CONTROL were very high, indicating that these were uninformative parameters with no true influence on model fit. After removing these terms, we generated a full model set with the remaining terms (Table 1). The top two models in this set accounted for 97% of model weights and included only DOSAGE+SEX+DOSAGE*SEX or those terms +CI. Most snakes (70.7%) succumbed between 24 and 48 hours after ingestion of acetaminophen treatments, consistent with results from prior brown treesnake studies (Savarie et al. 2000;Nafus and Siers 2017), and 50% of lethally intoxicated snakes died by 36 hours. DOSAGE was a highly influential predictor of time to death, being included in models carrying ≃ 100% of AICc model weights, with the top model including DOSAGE being 32.41 AICc units lower than the top model without DOSAGE (p-value from the top model = 0.003). Snake sex affected survival times (p = 0.001), with females succumbing more slowly than males ( Figure 4A). There was a strong interaction between SEX and DOSAGE: males receiving a high dosage succumbed more quickly than females receiving the same dosage, but males receiving a low dosage also succumbed more slowly than females receiving that dosage ( Figure 4B). Snakes in poorer body condition succumbed more quickly than snakes that were heavier for their length ( Figure 4C), but the effect was modest; this term was included in the top model carrying 68% of model weights, and the z-statistic suggested compatibility with an effect of CI (p = 0.084).

Regurgitation
Of the 116 dosed snakes that died, 97 (83.6%) regurgitated the mouse that contained the acetaminophen capsule. Time to regurgitation ranged from 9.7 to 80 hours after ingestion, with a mean time of 27.5 hours (SD ± 10.8). Time to regurgitation was highly correlated with time to death (F-statistic = 197.39, p << 0.001, adjusted R 2 = 0.672). On average, regurgitation occurred at 71.5% of the time interval between ingestion and death (SD ± 14.7%, range = 23 to 100%). In contrast, only 2/40 (5%) of snakes in the 0-mg treatment group regurgitated.

General Observations
After consuming a treatment mouse, snakes generally did not move from the corner of their container. Snakes that died were lethargic and unable to right themselves when flipped over onto their backs. Several snakes were

Discussion
Our results demonstrate that acetaminophen is a highly effective oral toxicant for California kingsnakes invasive to Gran Canaria, and that the 60-mg dose was sufficient to lethally intoxicate all 40 snakes in the treatment group. Table 2 summarizes how our methods and results compare to those of previous evaluations of acetaminophen toxicity to reptiles. In addition to methemoglobinemia brought about by liver damage, Mathies and Mauldin (2020) also found several serum enzymatic indicators of liver damage and indication of possible muscle damage in brown treesnakes treated with acetaminophen. Liver damage was also noted in chameleons lethally dosed with acetaminophen (Van Kleeck and Holland 2018). Extreme sensitivity of snakes to acetaminophen is based on a lack of genes coding for enzymes that are responsible for biotransformation of acetaminophen in other vertebrates; other reptiles also share this trait to a lesser extent, and all reptiles appear to have lower tolerance for acetaminophen than most mammals (Van den Hurk and Kerkkamp 2019). The heaviest snake in our study was 554 g; to reach the 133 mg/kg LD 99 , the snake would require a dose of approximately 74 mg. This snake was in our 80-mg treatment group and died, as did the next-heaviest snake (542 g) in the 60-mg group with a dosage of 111 mg/kg. The reported range of kingsnake masses reaches up to 2,268 g (Bartz 2012); at this mass, a kingsnake might be expected to need over 300 mg to be 99% confident of mortality. Within our sample, the heaviest snakes tended to be male (8 of 10 greater than 400 g). Fisher et al. (2019) found that adult California kingsnakes on Gran Canaria had greater body mass than those in their native range, with up to 23% greater average mass within the top decile compared to snakes caught in southern California. In their sample of 519 adult snakes from Gran Canaria, the heaviest was 770 g; an 80-mg tablet would equal a dosage of 104 mg/kg, and a dose of 103 mg would be required to put a snake of that size over the LD 99 of 133 mg/kg derived in this study. Fortunately, in experiments where a small number of larger brown treesnakes had survived ingestion of a dead newborn mouse (DNM) treated with 80 mg of acetaminophen, the survivors readily consumed another treated DNM a week later and all died (Nafus and Siers 2017). It is not yet known whether death after a second dose is a function of sampling variance (e.g., chance of surviving a 95% probability of death twice is only 0.25%) or whether there are lingering effects of the first dose that make snakes more susceptible to a subsequent dose.
Regurgitation of dosed bait mice does not increase probability of surviving. Based on the unreported data summarized in Table 2 (Savarie P, USDA, unpublished data), 26/104 (25%) of dosed brown treesnakes regurgitated (all of which died), compared to 83.6% of California kingsnakes in our study. This difference could be the result of some innate physiological differences between the two species; however, the USDA data also indicated that differences in tablet coating affected regurgitation rates. After controlling for survival and dosage (neither of which influenced regurgitation rates), snakes dosed with tablets that had an enteric coating regurgitated more frequently than those receiving uncoated tablets or tablets coated with beeswax (p = 0.001 and 0.039, respectively; logistic regression with Tukey's HSD test). It is possible that our higher rate of regurgitation is associated with the powdered form of acetaminophen in gel caps we used in this study. This difference appears not to influence efficacy, since both studies exhibited very high mortality rates. Our control treatment did not incorporate an inert powder into the placebo gelatin capsules; it is possible that regurgitation may have been caused by a release of powder into the digestive system irrespective of presence of the active ingredient. In practice, a high regurgitation rate may increase environmental risks if regurgitated baits still contain high concentrations of acetaminophen and are subsequently ingested by nontarget species.
Although a 60-mg dose was 100% lethal in our test group, the heaviest snake we tested at that dose was 542 g. While it is desirable to minimize toxic inputs into the environment, in order to ensure efficacy for rare larger snakes it may be prudent to consider the 80-mg uncoated acetaminophen tablets currently prescribed for brown treesnake control. A practical advantage of this approach would be that risk analyses and other test results amassed in support of the USEPA registration of acetaminophen for brown treesnake control might be accepted as part of a registration process for acetaminophen for control of other invasive snakes, including California kingsnakes in the Canary Islands.
The use of any product as a pesticide is likely to be strongly regulated by jurisdictional law. Our results should in no way encourage the use of any drug or pesticide in a manner inconsistent with the product label. Any California kingsnake or other invasive reptile control program must comply with all environmental and other applicable regulations of the appropriate jurisdictions, and any suspected misuse of a product for pesticidal applications should be reported to the appropriate authorities.
Managers confronting the brown treesnake invasion of Guam did not have an effective oral toxicant until well after the snake had invaded all habitats across Guam's landscapes and the greatest damages had already been caused. In that sense, mangers trying to stem the California kingsnake invasion of the Canary Islands have an advantage. However, while an integral tool in interdiction and control (Clark et al. 2018), and growing in utility as new application methods are devised (e.g., Siers et al. 2019), acetaminophen has not been a panacea for brown treesnake management in Guam. Nor do we suggest that it may be the solution for control of California kingsnakes in the Canary Islands. Nontarget risks are very limited on Guam (Johnston et al. 2002), while the fauna in the Canaries is more diverse and potentially susceptible to nontarget poisoning, such as buzzards (Buteo buteo Linnaeus, 1758), ravens (Corvus corax Linnaeus, 1758), invasive rodent species, and feral cats and dogs. Canary Islands have high rates of endemism (Emerson 2003), which may require increased caution when considering acetaminophen field use (especially if California kingsnakes have an increased regurgitation response to acetaminophen). Lizards on Gran Canaria are either frugivores or insectivores, so potentially the concern may be limited to Gran Canaria avian species.
With all invasive species concerns, there is no substitute for prevention. Prudent management of the California kingsnake invasion in the Canaries should begin with ensuring that the "contagion" is not spread to other islands and habitats. LIFE+ Lampropeltis's objectives were to research California kingsnake behavior, implement a capture program, inform the public, and advocate for increased regulation on animal imports. All the objectives were met, including influencing legislation to prohibit live or dead colubrid snake possession in the Canary Islands, Ibiza, and Formentera (Cabrera-Pérez et al. 2012), but meeting these objectives did not accomplish their main objective of eradicating or even reducing California kingsnake populations. Contrary to LIFE+ Lampropeltis's main objective, the most recent established population, Maspalomas, occurred during LIFE+ Lampropeltis's leadership and California kingsnake's populations continue to expand with snakes being found in new areas daily (LIFE+ Lampropeltis 2012). New priorities should be focused on port biosecurity to prevent California kingsnakes from island-hopping to other Canary Islands as has occurred on Guam for prevention of further spread of Brown Treesnakes (Clark et al. 2018). There are currently no plans, to our knowledge, to increase port biosecurity on Gran Canaria.
As with brown treesnake interdiction, acetaminophen baits may be a cost-effective tool to prevent spread off the island. However, unwarranted enthusiasm for acetaminophen as a control tool should not lend a false sense of confidence in the ability to protect native species at risk from California kingsnake predation (e.g., the Gran Canaria giant lizard) and proactive conservation measures should be taken to prevent extirpation. If nontarget risks are duly evaluated and mitigated, and if mitigation doesn't dilute more direct interdiction and conservation efforts, acetaminophen baits may be useful in reducing or eliminating California kingsnakes and the damage they cause in the Canary Islands.