Acetaminophen as an oral toxicant for nile monitor lizards (varanus niloticus) and burmese pythons (python molurus bivittatus)

University of Nebraska - Lincoln

Acetaminophen as an Oral Toxicant for Nile Monitor Lizards (Varanus niloticus) and Burmese Pythons (Python molurus bivittatus)Richard E. MauldinUnited States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, National WildlifeResearch Center, 4101 LaPorte Avenue, Fort Collins, Colorado 80521, USA, [email protected] Peter J. SavarieUnited States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, National WildlifeResearch Center, 4101 LaPorte Avenue, Fort Collins, Colorado 80521, USA Follow this and additional works at: Mauldin, Richard E. and Savarie, Peter J., "Acetaminophen as an Oral Toxicant for Nile Monitor Lizards (Varanus niloticus) andBurmese Pythons (Python molurus bivittatus)" (2010). USDA National Wildlife Research Center - Staff Publications. Paper 943.
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Wildlife Research, 2010, 37, 215–222
Acetaminophen as an oral toxicant for Nile monitor
lizards (Varanus niloticus) and Burmese pythons
(Python molurus bivittatus)
Richard E. Mauldin A,B and Peter J. Savarie A AUnited States Department of Agriculture, Animal and Plant Health Inspection Service, Wildlife Services, National Wildlife Research Center, 4101 LaPorte Avenue, Fort Collins, Colorado 80521, USA.
BCorresponding author. Email: [email protected] Context. Invasive species are a growing global problem. Biological invasions can result in numerous harmful impacts on
local ecologies, and non-native herpetofauna are frequently ignored. Nile monitor lizards (Varanus niloticus) and Burmesepythons (Python molurus bivittatus, recently reassessed as Python bivittatus bivittatus), have become established in southernFlorida. Both are large, semi-aquatic predators that pose serious threats to a variety of threatened and endangered species,as well as to the unique ecology of the area.
Aims. Acetaminophen (CAS#103-90-2), a lethal oral toxicant for the invasive brown treesnake (Boiga irregularis)
on Guam, was investigated as a possible toxicant in juvenile Burmese pythons and Nile monitors.
Methods. Dead neonatal mouse (DNM) baits containing 0, 10, 20, or 40 mg acetaminophen were force-fed to Nile
monitors, whereas DNM containing doses of 0, 20, 40, or 80 mg were freely consumed by Burmese pythons. Subjects werefrequently observed post-treatment for general condition and position, with special attention paid to activity (if any),behaviour, respiration, bleeding, emesis, ataxia, and mortality.
Key results. In Nile monitors, acetaminophen doses of 10, 20, or 40 mg resulted in 0, 50 and 100% mortality, respectively.
In Burmese pythons, doses of 20, 40, or 80 mg resulted in 14.3, 85.7 and 100% mortality, respectively. No mortality wasobserved in control individuals of either species. A negative correlation between dosage (mg kg–1) and time-to-deathwas observed in both species. Dosages ranging from 522 to 2438 mg kg–1 and 263 to 703 mg kg–1 were uniformly lethal tomonitors and pythons, respectively. Neither species exhibited signs of pain or discomfort following acetaminophentreatment.
Conclusions. Acetaminophen is an effective toxicant in juvenile Nile monitors and Burmese pythons. Further
investigation into acetaminophen toxicity in adults of these species is merited.
Implications. Although further investigation into adult lethal dosages and strategies to optimise bait deployment while
minimising secondary hazards is required, acetaminophen may have a role to play in the control of these invasive speciesin Florida.
Additional keywords: acetaminophen, Burmese python, Florida, invasive species, Nile monitor, Python molurus
bivittatus, Varanus niloticus.
competition (Enge et al. ). Among the most recent and Invasive species are one of the leading causes of worldwide visible additions to the list of successful invasive species in biodiversity loss (Pimentel ), and the recognition that Florida are the Nile monitor lizard (Varanus niloticus) and the such biological invasions are of global concern has occurred Burmese python (Python molurus bivittatus, recently reassessed only within the past 60 years (Elton The sheer number of as Python bivittatus bivittatus, Jacobs et al. ), both large harmful impacts that invasive species can inflict is both extensive carnivorous reptiles. The initial presence of both species in and alarming (Krause The problem is compounded southern Florida is probably the result of intentional releases when the invasive species is a reptile or amphibian, because by reptile dealers and pet owners or by accidental escapes from herpetofauna are frequently disregarded as unimportant or captivity. In their native habitats, both species are primarily ignored altogether (Krause ).
semi-aquatic although they are found in a wide variety of The state of Florida unwillingly plays host to the greatest environments, a characteristic that may also play a part in number of established non-indigenous amphibian and reptile their successful colonisation and range expansion in southern species in the United States (Butterfield et al. ), due in part to importation for the pet trade, subtropical climate, and The Nile monitor is a large African lizard that can reach lengths reduced populations of native species resulting in diminished up to 2 m. Agile, aggressive, intelligent, and readily commensal, This article is a U.S. government work, and is not subject to copyright in the United States.
Wildlife Research R. E. Mauldin and P. J. Savarie the lizard is a generalist predator that can swim, climb, run, and (Engeman and Vice ; Vice and Pitzler ; D. S. Vice, dig, facilitating the consumption of a wide array of marine, pers. comm., 2009). Savarie et al. () evaluated fresh water, terrestrial and arboreal prey, and is also known to acetaminophen in laboratory efficacy tests by free-feeding hunt cooperatively (Campbell ). Initially established and captive brown treesnakes (47–300 g) with a single dead, successfully breeding in Cape Coral, Florida, c. 1990 (Enge et al.
frozen/thawed neonatal mouse (DNM) containing tableted Nile monitors are expanding their range and are now acetaminophen doses of 0, 10, 20, 40, or 80 mg snake–1. The found in seven southern Florida counties (Florida Fish and 40-mg (n = 10) and 80-mg (n = 29) doses resulted in 100% Wildlife Conservation Commission Monitors pose a mortality; 67% mortality was observed with the 20-mg dose threat to the eggs and young of turtle species that are either (n = 9). No mortality was observed at the 10-mg dose (n = 8).
endangered or of special concern such as sea turtles, diamond- Because snakes in excess of 300 g could be encountered in the backed terrapins (Malaclemys terrapin) and gopher tortoises field, the 80-mg acetaminophen dose was chosen for use in (Gopherus polyphemus). They may also threaten populations subsequent field trials.
Savarie et al. ) suspended a series of bait cunicularia floridana), as well as the young of the American stations made of PVC pipe (10.2-cm diameter
20.5-cm alligator (Alligator mississippiensis) and endangered American length) in vegetation around the perimeter of each of six crocodile (Crocodylus acutus; Campbell ; Enge et al. unbounded plots (three treated, three control) of 6 ha each in The Burmese python is among the largest of the python adjacent forested areas on Guam. A DNM containing 80 mg of species, reaching lengths of 7 m and weighing as much as acetaminophen was placed in each of the bait stations on the 91 kg. The species has an extensive native geographic treated plots, and an unadulterated DNM was similarly placed in distribution, ranging from India and Nepal (small, disjunct each station on the control plots. Acetaminophen treatment populations), through most of south-eastern Asia into portions resulted in near-total elimination of brown treesnakes from of Indonesia (Barker and Barker Burmese pythons are treated plots compared with control plots (Savarie et al.
most often found in rainforests and marshy areas, and, being ). Because of its demonstrated effectiveness and accomplished swimmers, are strongly associated with water minimal hazard to non-target species such as land crabs (Barker and Barker ). When smaller, Burmese pythons (Savarie et al. ) and the endangered Mariana crow are also skilled climbers, but tend to be more terrestrial (Corvus kubaryi, Avery et al. ), acetaminophen was because increasing size makes climbing problematic (Murphy registered for use in controlling brown treesnakes in Guam by and Henderson ). They prey primarily on appropriately sized the US Environmental Protection Agency. As with live traps mammals and birds, which are killed by constriction. Burmese (Rodda et al. ; Tyrrell et al. ), DNM baits may not pythons were probably introduced into the wild in southern target smaller snakes and techniques for delivery of baits to Florida during the 1980s when they were first observed in the this subgroup of snakes need further investigation.
saline glades and mangroves of southern Everglades National The successful invasion of the brown treesnake on Guam and Park (ENP; Meshaka et al. Pythons have been found in at its devastating impact on the island's avifauna provides a least three southern Florida counties, and their range is expanding cautionary tale of the repercussions of delay in dealing with (Florida Fish and Wildlife Conservation Commission invasive predators (Savidge ). Effective tools and strategies Pythons are known to consume the endangered Key Largo are required to limit if not reduce or eliminate the nascent woodrat (Neotoma floridana smalli, Greene et al. and populations of Nile monitors and Burmese pythons in southern the possible expansion of the python's range southward into Florida. The study described in the present report represents an the Florida Keys threatens a large number of endangered species, initial investigation into the effectiveness of acetaminophen as a including the rice rat (Oryzomys palustris natator), the Lower control agent for these invasive reptiles.
Keys marsh rabbit (Sylvilagus palustris hefneri) and FloridaKey deer (Odocoileus virginianus clavium). Snow et al.
Materials and methods
() examined the stomach contents of pythons taken in or All research was conducted at the National Wildlife Research near ENP and reported finding cottontail rabbits (Sylvilagus spp.), Center (NWRC) in Fort Collins, Colorado, USA, and performed bobcats (Lynx rufus), raccoons (Procyon lotor), oppossums according to a protocol (QA-1496) approved by the (Didelphis spp.), alligators, and a variety of wading birds and Institutional Animal Care and Use Committee. Imported juvenile Burmese pythons farm-raised in Vietnam and Nile Currently, there are no established, systematic operational monitors wild-caught in Africa were obtained from Ballroom control methods for either of these reptiles. Nile monitors have Pythons South (Haines City, FL, USA). All arrived at the been successfully live-trapped (Campbell whereas NWRC in apparent good condition. On arrival, monitors attempts to live-trap Burmese pythons have not been effective were individually numbered, weighed and housed singly in a (Campbell ; USFWS Various federal and Florida 57-L aquarium (31.1
61
32.4 cm, with a screen top). Each state agencies have begun cooperating to develop control aquarium contained a water bowl (17.8 cm diameter) and a PVC strategies, and the use of toxicants may have a role in the hide tube made by cutting a 15.9-cm-long section of 15.2-cm- control of both species. Acetaminophen (CAS# 103-90-2) is diameter pipe in half lengthwise. A thin cardboard sheet was an effective oral toxicant for the invasive brown treesnake used as a substrate. Additional heat was provided by a 15-W heat (Boiga irregularis) and is used operationally in an integrated lamp placed above the aquarium at one end.
program by the US Department of Agriculture, Wildlife Each aquarium was then placed into a four-shelf rack that Services, to control the snakes on the island of Guam housed four aquariums per shelf. Cardboard partitions were Acetaminophen toxicity in lizards and pythons Wildlife Research inserted between aquariums to visually isolate each monitor.
mentioned previously, it was the minimum dose found to yield Juvenile Nile monitors cannot be sexed by probe or visual 100% mortality in similarly sized brown treesnakes. One to inspection (T. Campbell, DVM, Colorado State University, three days before treatment, monitors and pythons were pers. comm.), so sex was not determined.
weighed and weight ranked from lowest to highest in sets of Each python was individually numbered, weighed, sexed four. By using the online randomisation program (Research by probing the hemipenes, and housed singly in a clear, Randomize, each of polycarbonate-lidded box measuring 45.5
66.0
17.0 cm the four monitors/pythons in a ranked set were then randomly (Cambro Mfg. Co, Huntington Beach, CA, USA). Each box assigned to one of four experimental groups (control, 40 mg contained a water bowl (17.8 cm diameter), PVC hide tube acetaminophen, and two groups with doses to be determined).
(5 cm diameter
22 cm long) and sheet-paper bedding. Each Since the sex of each python was known, the weight-ranking box was loaded onto a four-shelf rack that housed three boxes procedure was performed separately for males and females in an per shelf. Additional heat was supplied by 30-W mylar substrate attempt to equalise the sex ratio in each experimental group.
heaters (Ultratherm, Scotland).
The results of the range-finding phase determined the two Both species were housed on opposite ends of an remaining acetaminophen doses used in the second phase of the environmentally controlled room measuring 3.75
14.1 m.
trial. If 40 mg produced 0% mortality, the next doses chosen The room was maintained at 30C and 55% relative humidity would be 80 mg and 160 mg. Conversely, if 40 mg resulted in with a 12 h light/12 h dark photocycle (lights on at 0700 hours 100% mortality, the next two doses would be 20 mg and 10 mg.
Mountain Standard Time (MST), off at 1900 hours MST).
If mortalities of >0% and <100% were observed, 20 mg and Monitors were fed a single mouse three times weekly, and, 80 mg doses would follow to bracket the initial 40-mg dose.
because of the wide range of lizard masses, fed either hairless Immediately before treatment, animals were reweighed to or furred neonate mice ranging in mass from 2.0 g to 4.2 g ( 4.7% provide accurate dosage calculations. Following treatment at of average lizard mass). Pythons were fed furred DNM between 0900 hours and 1100 hours, animals were observed twice weekly, ranging in mass from 3.8 g to 6.5 g ( 3.9% of every 2–3 h until 2300 hours, with observations resuming average python mass). Monitors were given a 3-week acclimation at 0900 hours the following day. During observation, the period before toxicity trials, whereas pythons, which took longer condition and position of the animal was recorded. Special to begin accepting food and eating regularly, were given 7 weeks attention was paid to activity (if any), behaviour, respiration to acclimate.
rate, signs of bleeding, emesis, ataxia or mortality. Animalsthat expired during the treatment period were weighed and Acetaminophen tablet preparation examined for any external abnormalities. The time at which Acetaminophen tablets were prepared by adding the appropriate mortality was observed was taken as the actual time-to-death amount of acetaminophen to fixed percentages of matrix (TTD). The post-treatment observation period lasted 7 days, at the ingredients, which included polyvinyl pyrollidone binder (2.8%), end of which, all surviving animals (except for controls) were terminated by CO2 inhalation, weighed and incinerated. Linear cellulose binder (17%) and dibasic calcium phosphate filler regression analysis of dosage against TTD was performed using (3.7%). Magnesium stearate (0.3%) and stearic acid (0.6%) were the PROC REG program (SAS Institute Inc., Cary, NC, USA).
included as tablet press lubricants. Tablets varied in size, ranging Monitor lizards from 3 to 7 mm in diameter and from 1 to 2 mm in width. Prior totreatment, a tablet containing the appropriate acetaminophen dose Monitors were fasted 1–3 days before treatment. During the (or DNM only, for controls) was inserted deep into the esophagous of acclimation phase, monitors were observed tearing, mangling or a pre-weighed DNM which was just large enough to accommodate dismembering their prey. To avoid possible acetaminophen loss, the tablet. DNM were chosen as the toxicant carrier to mimic the monitors were force-fed by inserting an avian oral speculum ingestion of an actual treated bait. Both species were fed size- into the mouth and pushing until the mouth opened widely. The appropriate DNM which were as small as possible to minimise dosed, size-appropriate DNM was then inserted into the throat, possible tissue mass-related interference with acetaminophen the speculum was removed, the throat was gently massaged to release and absorption. Chemical analysis of five samples each of push the DNM towards the stomach, and the monitor was returned the 0-, 10-, 20-, 40- and 80-mg tablets yielded actual to its cage. DNMs ranged in mass from 2.0 to 4.7 g. To minimise mean  s.d. acetaminophen content of 0, 10.1  0.62, 19.0  1.1, disturbance, monitors hiding under the paper substrate were 39.5  0.90 and 77.1  2.6 mg, respectively. Dosage calculations observed with a mirror placed under the aquarium, aided by a (mg acetaminophen per kg body mass) were based on the actual ashlight when observations were made in darkness. There were determined dose.
eight monitors for each of the four doses (0, 10, 20 and 40 mg)tested.
Burmese pythons Pythons were fasted 3–7 days before treatment. On Because the response of both monitors and pythons to treatment day, each python was weighed and returned in its acetaminophen was unknown, toxicity testing in both species respective box to allow recovery and relaxation from handling.
required an initial range-finding phase, utilising a control Treated or control DNM were then offered on tongs, and were group and a single treatment group that received a 40-mg usually taken and consumed immediately. If the DNM was acetaminophen dose. This dose was chosen because, as refused, it was placed near the python and observed every Wildlife Research R. E. Mauldin and P. J. Savarie Acetaminophen dose-related mortality and approximate time-to-death data (mean þ s.d.) in Nile monitors
Values in parentheses are ranges Dosage (mg acetaminophen per kg body mass) time-to-death (h) 65.6 ± 32.0 (21.0–106) 73.0 ± 42.3 (23.5–150) 199 ± 138 (67.5–430) 66.8 ± 34.4 (19.7–122) 406 ± 300 (155–965) 55.1 ± 33.9 (31.3–95.0) 62.1 ± 32.7 (16.2–105) 934 ± 723 (377–2438) 27.3 ± 8.6 (23.8–48.5) 2–3 h to determine the actual consumption time. Uneaten DNM the lizards in both the 20-mg and 40-mg groups vomited the were left in the box overnight, and, if not consumed by the partially digested treated DNM just before death. Linear following morning, were replaced with a fresh control/treated regression analysis of dosage against TTD yielded the DNM. If a DNM had not been consumed within 3 days, the python equation y = –0.0176x + 50.7, with a P-value of 0.114 and an was force-fed a fresh control/treated DNM. DNMs ranged in mass associated r2 of 0.231. The regression is depicted in Fig. from 3.8 to 6.5 g. The acetaminophen doses tested and associatedgroup sizes were 0 (n = 5), 20 (n = 7), 40 (n = 7) and 80 mg (n = 7).
Burmese pythons Results of acetaminophen toxicity testing in Burmese pythons are summarised in Table . The 85.7% mortality observed Nile monitors with the 40-mg dose resulted in subsequent trials utilising80 mg and 20 mg. The 80-mg dose yielded 100% mortality, whereas the 20-mg dose resulted in 14.3% mortality. Dosages approximate TTD data in Nile monitors are summarised in from 263 to 703 mg kg–1 (X ¼ 458  140 mg kg–1) were lethal, Table . The 100% mortality observed with the 40-mg dose regardless of the dose administered. Regression analysis of resulted in subsequent trials utilising 20 mg and 10 mg. The dosage by TTD produced the equation y = –0.0423x + 50.0, 20-mg dose yielded 50% mortality; no mortality was observed with an associated r2 of 0.495 and a significant P-value of 0.005 (see Fig. ).
Acetaminophen dosages were highly variable within groups, with much overlap among groups. In many instances, a dosageresulted in mortality at one dose whereas a similar dosage at a different dose did not. Dosages of 204.3 and 228.6 mg kg–1, as y = –0.0176x + 50.7 R2 = 0.231 well as 788.4 and 964.5 mg kg–1 yielded mortality in the 20-mg dose treatment, whereas dosages ranging from 199.6to 429.8 mg kg–1 in the 10-mg dose treatment were not lethal.
All acetaminophen dosages from 522 to 2438 mg kg–1 (X ¼ 1056  651.4 mg kg–1) were lethal to juvenile monitor Treated monitors behaved similarly to controls, with no overt signs of pain or discomfort. No bleeding or ataxia were Time-to-death (h) observed. Most monitors crawled under the cardboard substrateand slept, and many died in the resting positions assumed following treatment. Basking under the heat lamp was also frequently observed. Respiration rates in all monitors were typically slow, and, along with activity, appeared to increase in response to the proximity of the observer. Extreme lethargy and Acetaminophen dosage (mg kg–1) unresponsiveness were observed just before death in severalmonitors from the 20-mg and 40-mg treatment groups, but not Regression of acetaminophen dosage by time-to-death (h) in Nile in controls or monitors from the 10-mg dose. Roughly half of Acetaminophen dose-related mortality and approximate time-to-death data (mean þ s.d.) in Burmese pythons
Values in parentheses are ranges Dosage (mg acetaminophen per kg body mass) time-to-death (h) 138 ± 40.2 (102–199) 118 ± 24.6 (78.7–149) 167 ± 37.3 (128–241) 133 ± 27.8 (89–165) 310 ± 74.6 (239–445) 35.7 ± 9.7 (22.8–47.2) 146 ± 29.2 (127–191) 546 ± 105 (403–703) 26.8 ± 6.0 (21.0–30.5) Acetaminophen toxicity in lizards and pythons Wildlife Research in monitors. This may have been due to the misleading nature y = –0.0423x + 50.0 of the TTD values when mortality was observed during the first R2 = 0.495 observation of the morning. Because that observation time was given as the TTD, it obscured the possibility of overnightmortality occurring as much as 10 h earlier. This situation was prevalent in TTD estimates at the 40-mg dose level inmonitors. Average mortality was given as 27.3 h, althoughsix of eight lizards probably died earlier than reported. The significant correlation found in pythons was aided by thedecreased variability in body mass range, which led to much Time-to-death (h) less variation in the dosage range within a given acetaminophendose. The decreased mass range was the result of similar originand ages of the juvenile pythons, whereas with wild-caught juvenile Nile monitors, the variable weights were probably aresult of differing ages.
The mechanism of acetaminophen toxicity in reptiles is not known, although it may be due to liver and kidney toxicity (National Acetaminophen dosage (mg kg–1) Toxicology Program possibly via glutathione depletion,which can lead to hepatic necrosis (Gosselin et al. Another Regression of acetaminophen dosage by time-to-death (h) in possibility is the occurrence of methemoglobinemia, which has Burmese pythons.
been observed in cats that have ingested acetaminophen (Fincoet al. Methemoglobinemia is a condition in which a larger As with the monitors, treated pythons behaved similarly to than normal percentage of circulating hemoglobin occurs as controls, and no overt symptoms of post-treatment pain or methemoglobin, a form of hemoglobin that does not carry discomfort were noted. No bleeding or ataxia was observed, oxygen. Acetaminophen-treated brown treesnakes also displayed and both respiration and activity was stimulated by observer severe methemoglobinemia (T. Mathies, unpubl. data).
presence. Pythons were most frequently observed coiled invarious parts of the box, or in the hide tube.
Treated pythons were frequently observed to be sluggish and Extrapolating lethal acetaminophen doses unresponsive before death, and many pythons that had been Further research is required to determine acetaminophen dosages coiled and resting for the entire post-treatment period were that would be consistently lethal to pythons and monitors at adult often seen crawling around the box periphery immediately masses. Whether effective and practical doses for use in adult before expiration.
monitors or pythons can be predicted by scaling up the doses Several pythons in the 40-mg group appeared bloated before employed herein, by using an isometric/allometric weight death, and this condition was even more pronounced in the 80-mg relationship also remains to be explored. In pythons collected dose group. Necropsy examination of a few of these individuals in or around the ENP between January 2003 and March 2006, revealed that the trachea and lungs were partially filled with clear, Snow et al. () found that the mean mass of males (n = 27) was colorless, semi-viscous fluid. Anterior pulmonary hemorrhaging 8.30  1.23 kg, and the mean mass of females (n = 29) was was also noted in one python.
12.1  2.10 kg. The overall weighted mean body mass of thesesnakes was 10.3 kg. Hypothetically, scaling isometrically from the data in the current report, multiplying the average adult The acetaminophen doses of 40 mg and 80 mg, which resulted in python body mass of 10.3 kg by the mean lethal dosage in total or near-total lethality for both monitors and pythons, were virtually identical to the 40-mg and 80-mg doses shown to be 458 mg kg–1
10.3 kg = 4717 mg (4.72 g) acetaminophen, a completely effective in brown treesnakes of similar weights.
dose that could be lethal to the average adult python found at Treated monitors/pythons displayed no apparent signs of ENP. If, however, dose effectiveness follows an allometric suffering or distress; similarly, no signs of discomfort were scaling of metabolism (i.e. mass-specific metabolic rates exhibited by treated brown treesnakes (P. J. Savarie, unpubl.
decrease with increasing body mass), less acetaminophen data). Interestingly, the emesis noted in monitor lizards was also could be used. Secor and Diamond calculated a body observed in several brown treesnakes treated with 40 and 80 mg of mass scaling exponent of 0.9 when measuring peak VO2 (aerobic acetaminophen (Savarie et al. ), but only one python in the capacity) during digestion for Burmese pythons fed meals equal 80-mg dose group vomited the treated DNM. In both monitors to 25% of the snake's body mass. If applied to the mean ENP and pythons, mortality fell off sharply with decreasing dose, python mass of 10.3 kg cited previously, the expression becomes decreasing from 100% to 0% with doses of 40 mg and 10 mg, 458 mg kg–1
10.30.9 kg = 3737 mg (3.74 g) acetaminophen to respectively, in monitors, and from 85.7% to 14.3% with doses of achieve lethality in an average adult python. Using the exponent 40 mg and 20 mg, respectively, in pythons.
derived from measuring VO2 during digestion seems particularly Linear equations produced by regression analysis of dosage applicable, because the toxicant would likely be delivered in a by TTD were remarkably similar. A negative correlation of consumable prey item, requiring digestion to mobilise the dosage with TTD was significant in pythons but not significant Wildlife Research R. E. Mauldin and P. J. Savarie Acetaminophen acute oral toxicity to a variety of mammal and bird species
Dosage (mg kg–1) and result House mouse (Mus musculus) Starmer et al. Bousquet et al. ( Norway rat (Rattus norvegicus) Ekwall et al. ) Boxill et al. ) Guinea-pig (Cavia cobaya) Boxill et al. ) Brushtail possum (Trichosurus vulpecula) 2000 – no mortality Eason et al. ( Northern bobwhite quail (Colinus virginianus) 2250 – no mortality Gallager and Beavers ( Fish crow (Corvus ossifragus) 80 mg bird–1 – 0/5 died Avery et al. ) 160 mg bird–1 – 1/5 died Body mass data collected from 200 adult Nile monitors research remains to be conducted using adult pythons and sampled around Cape Coral, Florida, indicated that most monitors to clarify these issues and provide relevant dose data weighed between 1 and 3 kg, with a mean of 2 kg for accurately assessing non-target risk concerns. However, an (T. Campbell, pers. comm.). A hypothetical isometrically initial discussion of possible acetaminophen deployment scaled adult-monitor lethal-dose prediction using the mean methods and presentation issues is appropriate as a general introduction to some of the questions that remain to be previously and the average adult-monitor mass of 2 kg yields a resolved for baiting Nile monitor lizards and Burmese pythons.
lethal adult-monitor dose of 2112 mg (2.11 g) acetaminophen.
It is useful to remember that doses of any toxicant must Estimation of an allometrically scaled adult-lizard dose utilises be delivered in a palatable, attractive bait. Delivery of the mass scaling standard metabolic rate exponent of 0.84 acetaminophen in carcasses of medium-to-large (0.5–2 kg) obtained by Secor and Phillips These authors studied frozen, thawed mammals such as rabbits or piglets would metabolic responses of the white-throated monitor lizard serve to limit availability to non-target species simply by prey- (Varanus albigularis), a lizard that, like the Nile monitor, size constraints. This would also select for size cohorts within occurs in central and southern Africa. When applied to the the target species large enough to take larger baits, especially if mean monitor-lizard mass of 2 kg cited previously, a corrected the target species consume the treated-bait whole. Further, average adult lizard mass of 1.79 kg results. Multiplying 1.79 kg acetaminophen would likely be inserted as a bolus deep within by 1056 mg kg–1 yields an estimated adult lethal dose of 1890 mg the body cavity of the treated carcass, further isolating the toxicant (1.89 g) acetaminophen.
from potential scavengers.
As stated previously, the mean lethal dosage used in the Placement of treated baits, such as suspension from a branch preceding calculations represents the average of a range of or held off the ground on a pole or attached to a tree trunk could serve as a further non-target barrier. Such placement might overestimate the actual lethal dose required. These values for have the additional advantage of requiring climbing ability acetaminophen lethality in adult pythons and lizards are highly (which both target species possess) to access the bait, which speculative and should be regarded as a guide for further would limit availability to large non-targets unable to climb experimentation and not as an operational prescription.
significant heights, such as crocodilians. Treated bait carcassescould also be placed in suspended/elevated PVC tubing ofappropriate length and diameter, which would limit access by non-targets with wide heads or short limbs, and might also serve Although acetaminophene toxicity has now been demonstrated in as an attractive shelter to pythons and monitors that could enter three species of reptiles, i.e. brown treesnakes, Nile monitors, and easily by virtue of narrow heads and necks (D. Beard, pers. comm.
Burmese pythons, it is usually less toxic to endotherms. 2009). In an operational setting, manipulating combinations of summarises the acute oral toxicity of acetaminophen in a variety treated-bait size and presentation could serve to limit non-target of mammal and bird species.
hazard dramatically. These approaches are by no means all- Accurate risk assessment calculations of primary and encompassing; however, they serve as a starting point for secondary hazards to non-target species require data on the toxicant dose or expected toxicant concentrations in a Obviously, extensive research into target size–acetaminophen particular situation (e.g. used in a bait). Johnston et al. () dose relationships, minimising secondary hazards, and eventual found that the use of acetaminophen-treated mouse baits to methods of deployment will be required before acetaminophen control the brown treesnake on Guam posed minimal non- can be considered for use in the control of Burmese pythons or target risks when weighed against the known damage inflicted Nile monitors in southern Florida.
by the invasive snake. In that case, extensive prior laboratory and field research had led to the point that these authors knew how thetoxicant was going to be deployed and the acetaminophen concentrations to be expected (Shivik and Clark Savarie Acetaminophen is an effective toxicant in juvenile Nile monitors et al. , The initial and limited results in the and Burmese pythons when administered in a DNM. An 80-mg present study are inadequate for this purpose, and substantial dose resulted in 100% mortality in monitors ranging in mass from Acetaminophen toxicity in lizards and pythons Wildlife Research 16.2 to 105 g, whereas 40-mg and 80-mg doses yielded 85.7% Elton, C. S. (1958). ‘The Ecology of Invasions by Animals and Plants.' and 100% mortality, respectively, in pythons ranging in mass (Methuen: London.) from 89 to 191 g. Dosages ranging from 522 to 2438 mg kg–1 and Enge, K. M., Krysko, K. L., Hankins, K. R., Campbell, T. S., and King, F. W.
263 to 703 mg kg–1 were uniformly lethal to monitors and (2004). Status of the Nile monitor (Varanus niloticus) in southwestern
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pythons, respectively. An inverse relationship between dosage and TTD was observed, and no signs of pain or discomfort during Engeman, R. M., and Vice, D. S. (2001). Objectives and integrated approaches intoxication were noted. Although extensive further investigation for the control of brown tree snakes. Integrated Pest Management is required to ascertain appropriate lethal dosages in wild adult Reviews 6, 59–76. doi:
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Care Staff at the National Wildlife Research Center in accommodating and Gosselin, R. E., Smith, R. P., and Hodge, H. C. (1984). ‘Clinical Toxicology caring for these animals. We also thank Christi Yoder for performing the of Commercial Products.' (Williams and Wilkins: Baltimore, MD.) statistical analyses, Jerry Hurley for the preparation of acetaminophen tablets, Greene, D. U., Potts, J. M., Duquesnel, J. G., and Snow, R. W. (2007).
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Manuscript received 26 November 2008, accepted 27 January 2010

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