Nobody Knew How It Worked: Repellent Mechanism, and Why the Best Product Against Mosquitoes Is the Worst Against Ticks

1. Introduction: the product nobody could explain

Repellents are the most widely used personal pest control product in existence, sold in every pharmacy, applied to children, and recommended by public health agencies.

Until recently nobody could say how the commonest one worked.

1.1 Why this belongs in a Manitoba journal

Because mosquitoes, blacklegged ticks and black flies all occur here and this journal has covered each, and §15 shows that the right product differs between them in a way most people have never been told.

It is also the only pest control decision most households make for themselves, standing in an aisle, with no information beyond a percentage.

2. What a repellent is not

A distinction worth making before anything else.

It is not a barrier and it is not a toxicant. It interferes with the insect's ability to locate you, which is why the whole question is about chemoreception rather than about toxicology.

2.1 What the insect is doing

Insects that feed on people are required to deploy an array of sensitive chemoreceptor networks that work in specific coordination to locate prey.⁸

A repellent attacks that coordination. This journal's articles on pheromone traps and on aggregation behaviour dealt with the same sensory system being exploited in the other direction, to attract rather than to confuse.

2.2 Why that makes it hard to test

A toxicant is assessed by counting dead insects. A repellent has to be assessed by counting bites that did not happen, which requires a person, a defined exposure and a strict endpoint, and §12.1 is what the field settled on.

2.3 The exception on the list

Permethrin, which appears in every repellent recommendation, is not a repellent. It is described as the toxicant permethrin on clothing,⁶ and §19 deals with it separately because it works on an entirely different principle.

3. The admitted gap

How plainly the field states its own ignorance.

The modes of action and molecular targets are poorly understood, and addressing the gap has become an urgent matter in order to understand how to improve the effectiveness of repellents and to develop a novel generation of olfactory disruptive compounds.¹

Of picaridin specifically: its method of action is not well understood; however, it is believed to be similar to that of DEET involving interference with an insect olfactory system.⁵

3.1 Why this is unusual

Most registered pesticides have a named mode of action and an assigned group, which is the whole basis of the rotation strategy this journal examined. Repellents do not fit that framework, because the target was unknown when they were registered.

3.2 Believed to be similar

That is the strength of the claim about a registered product sold worldwide, and it is an honest statement rather than an evasion.

This journal has generally found trade material more confident than the science behind it. Here the science is candid and the confidence appears downstream.

4. Why the gap mattered commercially

The practical consequence of not knowing the target.

Alternative compounds have been developed using molecular modeling, but the lack of knowledge of the molecular target or targets for DEET has retarded progress towards low cost alternatives.⁵

4.1 Why that follows

Rational design of a compound requires knowing what it is supposed to bind. Without a target, the search reverts to screening candidates empirically, which is slow and expensive.

This journal's article on sequence-based pesticides described the opposite case, where knowing the target precisely was the whole design. Here the absence of a known target is stated as the reason a cheaper product has not arrived.

4.2 Why cheaper matters

Repellents are important prophylactic tools for travelers and populations living in endemic areas of malaria, dengue, encephalitis, and other vector-borne diseases, and although DEET is described as low cost, more affordable alternatives are highly desirable, particularly for those in endemic areas where cost is an impediment.⁵

5. The two models

What the argument was about.

One account had the repellent acting as an odour the insect finds aversive. The other had it blocking the insect's ability to detect the host. These make different predictions and were treated as alternatives.

5.1 The everyday version of the disagreement

Does the repellent make you smell repulsive, or does it make you smell like nothing? Those are different claims about what a mosquito experiences, and people have asserted each confidently for sixty years.

5.2 Why both were plausible

Behavioural observation cannot easily distinguish them, because an insect that has stopped approaching looks the same whether it is avoiding something or has lost the trail.

Resolving it required moving from the animal to the receptor, which is §6.

6. The experiment

The design, which is elegant.

Researchers characterised the action of these repellents on two Aedes aegypti odorant receptors, AaOR2 and AaOR8, individually co-expressed with the common co-receptor AaOR7 in Xenopus oocytes.¹

6.1 What that setup does

It removes the insect. A single receptor is expressed in an amphibian egg cell, where its electrical response to a compound can be measured directly, with no behaviour, no other receptors and no confounding.

The question stops being what does the mosquito do and becomes what does this receptor do, which is answerable.

6.2 The compounds tested

DEET, IR3535, picaridin, and 2-undecanone, the last of which was incorporated in a commercial repellent for its repellent properties on various arthropods.¹

7. What it found

The results, which are strange enough to be worth setting out in full.

In the absence of odorants, DEET activates AaOR2 but not AaOR8, while 2-U activates AaOR8 but not AaOR2; IR3535 and Picaridin do not activate these ORs. In the presence of odors, DEET strongly inhibits AaOR8 but not AaOR2, while 2-U strongly inhibits AaOR2 but not AaOR8; IR3535 and Picaridin strongly inhibit both ORs.¹

7.1 What in the absence of odorants tests

Whether the compound is itself a signal. A receptor firing with nothing else present is detecting the repellent as an odour in its own right.

And in the presence of odours, the test is whether the compound prevents the receptor responding to the thing it exists to detect. Two different questions, which is why both conditions were run.

7.2 Reading that carefully

DEET switches one receptor on by itself, and switches the other off when its proper odour is present. Two opposite effects, from the same compound, on two receptors in the same animal.

7.3 And the other two behave differently again

IR3535 and picaridin activate neither receptor and inhibit both.¹ They are pure blockers in this system, where DEET is both a signal and a blocker.

Which means the three compounds people treat as interchangeable are doing measurably different things, and §15 shows that difference surfacing in field performance.

8. The reconciliation

The conclusion, and why it settles the argument.

The data demonstrate that repellents can act as olfactory agonists or antagonists, thus modulating OR activity, bringing concordance to conflicting models.¹

8.1 Both models were right

The smells-bad model was describing agonism at one receptor. The blocks-detection model was describing antagonism at another. They were not competing accounts of one phenomenon; they were partial accounts of two.

That is a satisfying resolution and a reminder that an apparent contradiction in a literature is sometimes two correct observations of different things, which is a pattern this journal has now met in the rotation and disclosure articles as well.

9. Why the two receptors were chosen

A detail that makes the result mean more.

The receptors are respectively activated by the odors indole and 1-octen-3-ol, odorants used to locate oviposition sites and host animals.¹

9.1 Indole and octenol are familiar

Both are standard attractants in vector surveillance, used to bait the traps that this journal's articles on West Nile monitoring and on pheromone trap interpretation described.

So the experiment took two compounds already known to pull mosquitoes into traps and asked what repellents do to the receptors that detect them. That is a well-chosen pair rather than an arbitrary one.

9.2 One receptor for finding you, one for finding water

Octenol is a host cue, present in breath and skin emanations, and this journal's article on pheromone trap interpretation noted it as a standard attractant in mosquito surveillance. Indole relates to finding somewhere to lay eggs.

So the receptor DEET inhibits in the presence of its odour is the host-finding one, which is exactly the channel a repellent would want to block. The choice of receptors was not arbitrary.

10. Odorant and tastant

A second route that complicates the picture usefully.

DEET acts at a distance as an odorant as well as by direct contact, i.e., as a tastant, although DEET reception is primarily mediated by the olfactory system. There is unambiguous evidence that olfactory receptor neurons are involved, and that an odorant receptor co-receptor Orco is essential for DEET reception.⁵

10.1 Two routes, one primary

Smelled at a distance, and tasted on contact.⁵ The second explains why an insect that lands on treated skin may still leave without biting.

10.2 Why Orco matters

It is the common co-receptor that partners with every odorant receptor in the insect, and the experiment in §6 used its equivalent. If it is essential for reception, then the effect runs through the standard olfactory pathway rather than through anything exotic.

11. The single target objection

An argument from the patent literature, which we include with reservations.

One filing asserts that these compounds stimulate a key receptor of the mosquitoes chemosensory array to illicit a repellent response, and that affecting one receptor proves to be its own limitation because the mosquito can still rely on other chemosensory receptors to locate prey.⁷

11.1 Our reservation

The filing names a receptor pair that does not obviously match the mosquito literature, and it is written to establish the merits of an invention. We would not rely on its specific claims.⁷

11.2 Why we include it at all

Because the redundancy argument explains something the efficacy data shows: protection times are measured in hours and no repellent is described as complete. A partial blockade of a redundant sensory system is what that looks like.

11.3 The underlying point is sound anyway

An organism with redundant sensory channels is harder to blind than one with a single channel, and §7 shows the repellents acting on a small number of receptors out of a large array.

That would predict incomplete protection rather than absolute protection, which is exactly what §12 measures.

12. Protection times against mosquitoes

The efficacy data, from a systematic review.

The review reports that the most effective asset was 80 per cent DEET with 420-minute protection time but used at a very high concentration, with risks of adverse effects, followed by 20 per cent picaridin with protection time of 410.4 minutes, 20 per cent DEET with protection time greater than 380 minutes, 15 per cent IR3535 with protection time of 362 minutes, 10 per cent IR3535 with 356-minute protection time, and 10 per cent picaridin with protection time of 351.5 minutes.²

12.1 What complete protection time means

The interval from application until the first bite. It is a strict endpoint and it is not the same as the product ceasing to work, since partial protection continues afterwards.

That makes the figures conservative, and it makes them comparable, which is why the measure is used.

12.2 The units are hours, not days

The best figure in that list is seven hours.² A person outdoors from morning to evening needs to reapply, and a product applied at breakfast is not working at dinner.

13. What that comparison implies about concentration

The most useful number in the article, and it is a comparison rather than a single figure.

Eighty per cent DEET gives 420 minutes. Twenty per cent picaridin gives 410.²

13.1 Why concentration is not dose

A repellent works at the skin surface, so what matters is how much active is present there and for how long, which is a function of evaporation rate and formulation as much as of the starting percentage.

A higher concentration puts more on at the start and does not necessarily keep more there, which is the mechanism behind the flat curve in §13.2. That reasoning is ours.

13.2 A quarter of the concentration, the same protection

Those are different compounds, so this is not a statement about DEET concentration. It is a statement about what is achievable at a much lower loading with a different active, and it is the comparison a purchaser is never shown, because the two products sit on the shelf advertising numbers that are not on the same scale.

The review itself flags the high concentration as carrying risks of adverse effects.²

13.3 And within DEET

Eighty per cent gives 420 minutes and twenty per cent gives over 380.² Quadrupling the concentration bought perhaps ten per cent more time.

Diminishing returns are steep, which is why guidance recommends DEET at a 20 to 30 per cent concentration rather than the highest available.⁴ That inference is ours; the sources give the figures without drawing the conclusion.

13.4 The recommended concentrations

One guide recommends picaridin at a 20 per cent concentration, DEET at a 20 to 30 per cent concentration, IR3535 at a 20 per cent concentration, or Oil of Lemon Eucalyptus at a 30 to 40 per cent concentration.⁴

14. Protection times against ticks

The same four compounds, a different target.

A 2013 review of efficacy against deer ticks lists a mean protection time of 7.2 hours for IR3535, 3.5 hours for DEET, 2.7 hours for Oil of Lemon Eucalyptus or PMD, and 2.5 hours for picaridin.⁴

Two studies indicate that IR3535 repels deer ticks as well as or better than DEET.⁴

14.1 How thin this evidence is

The same guide that reports those figures states that there are few peer-reviewed scientific studies of the efficacy of these chemicals against deer ticks.⁴

So the inversion in §15 rests on a smaller literature than the mosquito figures do, and the honest reading is that the tick ranking is less securely established rather than that it is wrong.

15. The inversion

The finding that should change how these products are sold.

Against mosquitoes, picaridin at 20 per cent is close to the best available and IR3535 is mid-table.² Against deer ticks, IR3535 is first at 7.2 hours and picaridin is last at 2.5.⁴

15.1 Why this is not obvious from the packaging

A bottle listing mosquitoes, ticks, black flies and biting midges together implies one performance against all of them. The evidence says otherwise and the label has no room to.

15.2 The ranking reverses completely

The best of the four for one target is the worst for the other. There is no single best repellent, and a person buying one product for a day that includes both mosquitoes and ticks is making a trade-off nobody has told them about.

15.3 Why it might reverse

Ticks are arachnids with an entirely different sensory apparatus from mosquitoes, detecting hosts through a specialised organ rather than through the antennal receptors in §6. A compound tuned to mosquito odorant receptors has no reason to perform equivalently on a tick.

The surprise is not that the rankings differ. It is that anybody expected them not to, given that the two groups last shared an ancestor several hundred million years ago.

That is our explanation and the sources do not offer one.

15.4 A third target

One retail guide reports that IR3535 may not offer as robust protection against mosquitoes compared to DEET and picaridin, and it may require more frequent application, but may be more effective against no-see-ums, blackflies and sandflies.³

Which is a third ranking again, and black flies are a significant seasonal nuisance in this province.

16. The lone star tick trial

A controlled comparison worth describing for its method.

Researchers tested a 20 per cent picaridin spray, 20 per cent IR3535 spray, 20 per cent picaridin lotion, 10 per cent IR3535 lotion, and 33 per cent DEET cream against nymphal lone star ticks, at 2-h intervals over 12 h using human subjects. A repellent formulation was applied in a 5-cm-wide band encircling a volunteer's lower leg, and for each challenge 70 host-seeking nymphs were released on each volunteer.⁹

16.1 The band design

A treated band around the leg, with ticks released below it, tests whether the repellent stops them crossing.⁹ That isolates the repellent effect from everything else about the person.

16.2 Seventy nymphs per challenge

Seventy ticks released per volunteer per challenge, repeated at two-hour intervals over twelve hours.⁹ That is a deliberately severe exposure, far heavier than an ordinary walk through vegetation.

A product that holds under that load is being tested harder than it will be used, which makes the result conservative in the right direction.

16.3 The result

In the formulations tested, deet, picaridin, and IR3535 provided lasting protection against the species, and the 10 per cent IR3535 lotion was significantly less effective than the formulations with higher concentrations of repellent.⁹

So concentration mattered at the bottom end even where §13 found it mattering little at the top.

17. The formulation finding

The result that most surprised us.

Formulation can play a critical role in extending repellent efficacy. For example, a liposomal formulation of deet provided complete protection on treated rabbits against attachment of adult ticks of two species for 72 h compared to no protection by a standard formulation of deet.⁶

17.1 What a liposomal formulation does

It encloses the active in lipid vesicles, which changes how quickly it evaporates from skin and how it is released over time. The compound is identical; its availability at the surface is not.

17.2 Seventy-two hours against none

Same active ingredient. Complete protection for three days from one formulation and no protection from the other.⁶

If that transfers to human products at all, then the percentage on the front of the bottle is a much weaker predictor of performance than everybody assumes, and the thing that matters is not disclosed.

17.3 The caution

Treated rabbits, two tick species, and a specialised formulation that may not exist in retail products.⁶ We are not claiming a consumer product does this.

We are claiming that a factor capable of producing that range exists and is invisible to the purchaser, and this journal's article on formulation and substrate reached the same conclusion about residual products.

18. Spray against lotion

The comparison people actually face in a shop.

In the tick trial, there was no difference in effectiveness between the 20 per cent spray and 20 per cent lotion formulations of picaridin.⁹

18.1 Why format could have mattered

A lotion is rubbed in and a spray is deposited, which plausibly changes how evenly the active covers the skin and how fast it evaporates. The trial found no difference, which is worth knowing precisely because the expectation was reasonable.

18.2 Which is reassuring as far as it goes

At matched concentration, in that species, over twelve hours, the format did not matter.⁹

Practical differences remain: a retail guide notes that spray is easier to apply on the move and to clothing, while some lotions last longer than their spray counterparts in the same concentration and are better for face application to avoid getting product in the eyes.³

18.3 Those two accounts are in mild tension

A controlled trial found no difference and a retail guide says some lotions last longer.⁹³ The trial tested specific products; the guide is a generalisation.

We would take the trial for the products it tested and treat the general claim as unestablished.

19. Clothing is a different problem

The permethrin question, which is not a repellent question.

Public health recommendations for prevention of tick bites are the use of a repellent containing 20 per cent or more deet on skin or the toxicant permethrin on clothing,⁶ with clothing and gear treated with 0.5 per cent permethrin described as a good way to prevent tick bites.⁴

And the comparison: available efficacy testing indicates that permethrin-treated clothing provides a higher level of protection from ticks than repellents applied to the skin.⁴

19.1 Note what the recommendation actually says

Repellent on skin, or toxicant on clothing.⁶ Two different products, two different mechanisms, and the guidance treats them as alternatives rather than as the same category.

19.2 The most important sentence for tick country

Treated clothing outperforms skin repellent against ticks.⁴ That is a different product category, bought in a different place, and it is the one the evidence favours.

19.3 The practical asymmetry

Treated clothing is applied once and lasts through washes; a skin repellent is applied every few hours by the person who is trying not to think about it.

Compliance is therefore built into one and not the other, which may be part of why the field comparison favours it and is a factor the trials do not capture. Our observation.

19.4 Why a toxicant works better here

A tick must crawl across clothing to reach skin, which gives a treated garment a long contact period. This journal's article on tick attachment duration established that the interval between contact and attachment is substantial, and permethrin acts during it.

A skin repellent has only the moment of arrival. That explanation is ours.

20. The botanical question

The category with the largest gap between perception and evidence.

Citronella oil, peppermint oil and other natural oils are considered of minimal risk but have not been evaluated by the EPA for effectiveness.³

20.1 The toxicity argument against botanicals

One patent filing asserts that the use of botanical extracts to repel mosquitoes has met with limitation due to the toxic effects of some of the chemicals that they contain.⁷

That is a commercially motivated claim and it is not entirely wrong: a plant extract is a mixture of many compounds, most of which have never been individually assessed. Natural does not mean characterised.

20.2 Minimal risk is not efficacy

A product exempted from registration on safety grounds has not been assessed for whether it works, and this journal's article on consumer pest products found the same structure behind several other categories.

20.3 The lemon eucalyptus confusion

Natural lemon eucalyptus oil is not the same as Oil of Lemon Eucalyptus.⁴

One is an essential oil and the other is a registered repellent derived from it. They sit on adjacent shelves under near-identical names, and only one has efficacy data behind it. A purchaser reading carefully still has no way to tell which they are holding without knowing the distinction in advance.

20.4 The safety exception worth knowing

PMD, the active in that registered product, exhibits low rat oral and rabbit dermal toxicity, but is exceptionally irritating to the eyes and can cause irreversible eye damage.⁶

That is a serious warning on a product marketed as the natural option, and it is the reverse of the assumption most purchasers make. Plant-derived and gentle are not the same property.

21. What we would recommend here

Match the product to the pest. The ranking inverts between mosquitoes and ticks.²⁴

Twenty per cent is the working figure. For picaridin, DEET and IR3535.⁴

Do not buy the highest percentage available. Quadrupling DEET bought about ten per cent more time.²

For ticks, treat the clothing. It outperforms skin repellent.⁴

Reapply. The best protection times are hours.²

Check the registration. Minimal risk is a safety category, not an efficacy one.³

And do not assume one product covers everything. The same bottle faces three different organisms with three different sensory systems.

22. Limitations and open questions

The two efficacy datasets are not comparable. One is a systematic review against a mosquito species and the other is a review of deer tick efficacy reported by an advocacy organisation. The inversion in §15 is real as reported and we have not verified that the two used comparable methods.²⁴

One source is advocacy and one is retail. An environmental organisation's consumer guide and an outdoor retailer's advice page, both cited as attributed material rather than as research.³⁴

Two sources are patent filings. Used for a regulatory recommendation, a formulation finding and a mechanistic assertion we have explicitly doubted.⁶⁷

The tick evidence base is thin. The advocacy guide itself states that there are few peer-reviewed scientific studies of the efficacy of these chemicals against deer ticks.⁴

The receptor work is one study on two receptors. A mosquito has many, and extending the reconciliation in §8 to repellent action generally is an inference rather than a demonstration.¹

The systematic review asks for better studies. Its own recommendation is to carry out new studies to compare the performance of repellent with reliability.²

No black fly data. The claim about IR3535 and black flies comes from a retail guide with no study cited, and black flies are a Manitoba problem we would like evidence on.³

Nothing on children, pregnancy or duration of use. Those are medical questions and belong to a physician or a public health authority rather than to us.

Sections 2.1, 4.1, 5.1, 6.1, 8.1, 9.1, 10.2, 11.2, 13.2, 15.1, 15.2, 17.1, 18.2, 19.2 and 20.1 are our reasoning. The sensory framing, the rational design argument, the indistinguishability of the models, the account of what the oocyte system does, the reconciliation reading, the receptor choice point, the Orco inference, the redundancy argument, the diminishing returns conclusion, the inversion reading and its proposed explanation, the formulation implication, the tension between two accounts, the contact time argument and the minimal risk point are ours rather than sourced positions.

23. Conclusion

The molecular targets of the commonest repellents are described in the literature as poorly understood, and the absence of a known target for DEET is stated as the reason cheaper alternatives have been slow to arrive.¹⁵ When the question was taken to isolated receptors, the answer turned out to be that DEET activates one and inhibits another, while IR3535 and picaridin activate neither and inhibit both, so that repellents act as olfactory agonists or antagonists and two models that had been treated as rivals were both describing something real.¹

What follows practically is less elegant and more useful. Twenty per cent picaridin performs close to eighty per cent DEET against a mosquito, and quadrupling DEET concentration buys around ten per cent more time.² Against deer ticks the order reverses entirely, with IR3535 first at 7.2 hours and picaridin last at 2.5.⁴ And a liposomal formulation of the same active that gave no protection as a standard formulation gave complete protection for seventy-two hours.⁶

So the number on the front of the bottle is the least informative thing about it. What matters is which active, against which organism, in what formulation, and for how long you actually need it. For ticks specifically the evidence favours treating the clothing rather than the skin, which is a different product entirely.⁴ None of that is on the label, and the percentage that is on the label is the one thing people compare.

References

1. Insect Repellents: Modulators of Mosquito Odorant Receptor Activity. PLOS ONE, reproduced at PubMed Central PMC2920324. Principal mechanistic source. Used for the statements that the exact modes of action and molecular targets of the active ingredients found in insect repellents are poorly understood, and that addressing this gap has become an urgent matter in order to understand how to improve the effectiveness of repellents and to develop a novel generation of olfactory disruptive compounds; for the note that most insect repellent products include DEET, IR3535, picaridin and 2-undecanone, the last of which was incorporated in a commercial repellent in 2007 for its repellent properties on various arthropods; for the experimental design characterising the action of these repellents on two Aedes aegypti odorant receptors individually co-expressed with a common co-receptor in Xenopus oocytes, those receptors being respectively activated by indole and 1-octen-3-ol, odorants used to locate oviposition sites and host animals; for the findings that in the absence of odorants DEET activates the first receptor but not the second while 2-undecanone activates the second but not the first, and IR3535 and picaridin activate neither, and that in the presence of odours DEET strongly inhibits the second but not the first, 2-undecanone strongly inhibits the first but not the second, and IR3535 and picaridin strongly inhibit both; and for the conclusion that these data demonstrate repellents can act as olfactory agonists or antagonists, thus modulating receptor activity and bringing concordance to conflicting models. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920324/
2. Efficacy of the DEET, IR3535, and Picaridin Topical Use Against Aedes aegypti: A Systematic Review. Infectious Diseases in Clinical Practice, 28(6), 327 to 341. doi:10.1097/IPC.0000000000000875. Used for the review's objective of determining the efficacy of topical insect repellents against that species, the search strategy and the use of a published quality checklist; for the reported results that the most effective asset was 80 per cent DEET with 420-minute protection time but used at a very high concentration with risks of adverse effects, followed by 20 per cent picaridin at 410.4 minutes, 20 per cent DEET at greater than 380 minutes, 15 per cent IR3535 at 362 minutes, 10 per cent IR3535 at 356 minutes and 10 per cent picaridin at 351.5 minutes; and for the authors' recommendation that new studies be carried out to compare the performance of repellents with reliability. https://journals.lww.com/infectdis/abstract/2020/11000/efficacy_of_the_deet,_ir3535,_and_picaridin.4.aspx
3. Insect Repellent Guide. Outdoor equipment retailer advice page. Retail source with a commercial interest, cited as attributed material. Used for the statements that studies have found IR3535 may not offer as robust protection against mosquitoes compared with DEET and picaridin and may require more frequent application, but may be more effective against no-see-ums, blackflies and sandflies; that citronella oil, peppermint oil and other natural oils are considered of minimal risk but have not been evaluated by the federal regulator for effectiveness; that labels should be checked to ensure products are registered, since registration also brings information such as suggested reapplication time and safe ages for children; and that spray is easy to apply on the move and on hard-to-reach areas as well as to clothing, while some lotions last longer than their spray counterparts at the same concentration and are better for face application to avoid getting product in the eyes. https://www.rei.com/learn/expert-advice/insect-repellents.html
4. Guide to Bug Repellents. Environmental advocacy organisation consumer guide. Advocacy source, cited as attributed material. Used for the statements that there are few peer-reviewed scientific studies of the efficacy of these chemicals against deer ticks and that two studies indicate IR3535 repels deer ticks as well as or better than DEET; for the reported 2013 review of efficacy against deer ticks listing mean protection times of 7.2 hours for IR3535, 3.5 hours for DEET, 2.7 hours for Oil of Lemon Eucalyptus or PMD and 2.5 hours for picaridin; for the report that in one study 33 per cent DEET, 20 per cent picaridin and 20 per cent IR3535 repelled lone star ticks for some hours while 10 per cent IR3535 did not; for the statement that clothing and gear treated with 0.5 per cent permethrin may be a good way to prevent tick bites and that available efficacy testing indicates permethrin-treated clothing provides a higher level of protection from ticks than repellents applied to the skin; for the recommended concentrations of picaridin at 20 per cent, DEET at 20 to 30 per cent, IR3535 at 20 per cent and Oil of Lemon Eucalyptus at 30 to 40 per cent; for the statement that no repellent is 100 per cent effective and the associated advice to cover up, consider treated clothing, check for ticks nightly and wash after application; and for the warning that natural lemon eucalyptus oil is not the same as Oil of Lemon Eucalyptus. https://www.ewg.org/consumer-guides/bug-repellents
5. Repository record of a systematic review of topical repellent efficacy, with associated discussion of mechanism. Used for the statements that repellents are important prophylactic tools for travellers and populations living in endemic areas of malaria, dengue, encephalitis and other vector-borne diseases; that DEET is a safe, broad spectrum repellent providing complete protection over a long period, and that despite its low cost more affordable alternatives are highly desirable particularly where cost is an impediment; that alternative compounds such as IR3535 and picaridin have been developed using molecular modelling but the lack of knowledge of the molecular target or targets for DEET has retarded progress towards low cost alternatives; that DEET acts at a distance as an odorant as well as by direct contact as a tastant although reception is primarily mediated by the olfactory system, with unambiguous evidence that olfactory receptor neurons are involved and that an odorant receptor co-receptor is essential for DEET reception; that picaridin's method of action is not well understood but is believed to be similar to that of DEET involving interference with an insect olfactory system; and for the suggestion in the literature that picaridin was a more effective repellent than DEET at similar concentrations and with lower toxicity. https://www.researchgate.net/publication/343301179_Efficacy_of_the_DEET_IR3535_and_Picaridin_Topical_Use_Against_Aedes_Aegypti_Systematic_Review
6. Arthropod control compositions and methods. United States patent specification, background section reviewing the repellent literature. Cited as attributed material. Used for the statements that IR3535 and picaridin are two alternatives to DEET exhibiting good aesthetic characteristics and low mammalian toxicity and are both registered pesticides; that PMD exhibits low rat oral and rabbit dermal toxicity but is exceptionally irritating to the eyes and can cause irreversible eye damage; for the reported public health recommendation for prevention of tick bites being use of a repellent containing 20 per cent or more DEET on skin or the toxicant permethrin on clothing; and for the account that formulation can play a critical role in extending repellent efficacy, with a liposomal formulation of DEET providing complete protection on treated rabbits against attachment of adult ticks of two named species for 72 hours compared with no protection from a standard formulation of DEET. https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/10149481
7. Insect repelling composition. United States patent specification, background section. Cited as attributed material and explicitly doubted in the text. Used for the assertions that insects preying on humans deploy an array of sensitive chemoreceptor networks working in specific coordination to locate prey; that DEET, IR3535 and picaridin are effective in that they stimulate a key receptor of the mosquito's chemosensory array to elicit a repellent response; that affecting a single receptor proves to be its own limitation because the mosquito can still rely on other chemosensory receptors to locate prey; and that the use of botanical extracts to repel mosquitoes has met with limitation due to the toxic effects of some of the chemicals they contain. https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/11246310
8. Insect repelling composition, related patent specification. Cited as attributed material for the statement that insects which prey on humans are required to deploy an array of sensitive chemoreceptor networks that work in specific coordination to locate prey, and for the assertion that affecting a single receptor creates a single method of repelling which leaves other chemosensory routes available. https://image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/11985973
9. Carroll, J. F., Benante, J. P., Kramer, M., Lohmeyer, K. H. and Lawrence, K. (2010). Formulations of Deet, Picaridin, and IR3535 Applied to Skin Repel Nymphs of the Lone Star Tick (Acari: Ixodidae) for 12 Hours. Journal of Medical Entomology, 47(4), 699 to 704. doi:10.1093/jmedent/47.4.699. Used for the context that although tick-borne pathogens can cause acute and chronic illnesses, implementation of area-wide tick control measures has been limited, so that by default personal protective measures such as applying repellents are the recourse for persons venturing into tick habitats, with permethrin-based products having been the standard for use on clothing; for the study design testing a 20 per cent picaridin spray, 20 per cent IR3535 spray, 20 per cent picaridin lotion, 10 per cent IR3535 lotion and 33 per cent DEET cream against nymphal lone star ticks at two-hour intervals over twelve hours using human subjects, with the formulation applied in a five-centimetre-wide band encircling a volunteer's lower leg and seventy host-seeking nymphs released on each volunteer for each challenge; and for the results that there was no difference in effectiveness between the 20 per cent spray and 20 per cent lotion formulations of picaridin, that the 10 per cent IR3535 lotion was significantly less effective than formulations with higher concentrations, and that in the formulations tested DEET, picaridin and IR3535 provided lasting protection against the species. https://academic.oup.com/jme/article/47/4/699/993002