Phenol toxicity is reported in cats, especially related to disinfectants and essential oils but a toxic dose is not usually indicated. Can its use be toxic to feline patients that need repeated administrations of a medication containing phenol as a preservative?
Hi
Phenol MLD after SC administration for cats is 80 mg/kg (see ref below). It means that MLD for 5 kg cat is 0.4 g / cat. If your medication contains 0.4% of phenol it means that MLD related to phenol will be around 100 g of the drug formulation at a single dose. Unfortunately have no data for oral dose so this calculation is biased. But it can be assumed that after po administration bioavailability could be lower than after sc so this value (100 g of the drug formulation) could be higher. Of course, it's still a very general "risk analysis" because your drug (active ingredient) probably also has some panel of ADRs.
If the total mass of your drug daily is lower than 5-10 g I think the risk is low but of course, possible tox interactions never could be completely excluded without analysis of drug metabolism and for example possible potentialisation of tox effects or ADRs. It should also be taken into account that animal is sick.
Unfortunately, there are no ideal drugs, but some are useful :)
https://books.google.pl/books?id=yoVHDwAAQBAJ&pg=PT180&lpg=PT180&dq=Susceptibility+of+cats+to+phenol&source=bl&ots=U0u5xUPbO_&sig=ACfU3U3Z5lb5fRxz5q3XWrLWk0LGyoXuNw&hl=pl&sa=X&ved=2ahUKEwjMuZm20qXxAhXP-6QKHR5xDykQ6AEwAnoECAYQAw#v=onepage&q=Susceptibility%20of%20cats%20to%20phenol&f=false
Best regards
Tomasz
This file may help you. I think not only the acute toxicity but also a chronic one should be taken into consideration.
Thank you very much Tomasz Grabowski for your answer. The medication I was talking about is allergen-specific immunotherapy and the route of administration is actually sublingual, even if in animals, some may be swallowed before oral mucosal absorption. The dose is very very low compared to the toxic dose you mention: 0,1-0,2 ml maximum, but it is daily and chronic for years or even lifelong, that's why I was concerned about acute but also possible cumulative toxicity. Especially in an animal with chronic kidney disease. I'm afraid there are no data about such a long low-dose exposure yet.
Thank you very much Kohei Torikai for the informations provided. As you say, chronic exposure may be a possible cause of toxicity which in the case of allergen-specific immunotherapy is important considering the potentially lifelong need for this kind of treatment. And in particular in cases where the animal has already chronic kidney disease for example.
Hi
I think in such doses real risk cumulation should be considered as low or very low. But toxicity not must be considered as low as well.
Sulphate conjugation is a major detoxication mechanism in the case of phenol in cats (not glucuronidation). If doses of phenol are high, this mechanism is easy saturated and then toxic effects of phenols are observed. In your case dose of phenol is extremely low so risko of saturation of this mechanism is probably low. Even if you analyse urine phenyl sulphate or phenol concentrations probably will be below any available LLOQ's. But of course, it cant be absolutely excluded. Finally, in this discussion, we should take into account that many drugs or "active compounds" may provoke some effects which could be completely different in relation to dose (a different mechanism). This is why the nature of ADR's in the case of very small doses may cover different groups of effects than in the case of high doses (close to MLD) doses.
Concluding that. A low level of cumulation (probably your case; risk assessment and additional analyses needed) not must rule out ADR's observation. Of course as you said and Kohei Torikai said may other factors like kidney dysfunction may have huge impact on final landscape of drug ADR's. Its really may complicate final assesment of the problem.
Best regards
Tomasz
Tomasz Grabowski it is very interesting to discuss this with you. So maybe the best approach would be to use this medication under regular control of clinical and lab parameters for this patients to detect any early signs of possible ADR.
Thanks again for your contribution.
Best regards
Beatrice
Hi,
It will be very informative if urine samples are analyzed. Collection of 2-3 samples per cat within the treatment period from many cats and observation of ADRs could be an excellent source of data for population analysis I hope. Maybe it will be some idea to analyze the link between the concentration of phenol or metabolites in urine and covariates like ADR's. In the beginning, it is necessary to check whether the concentration of phenol or metabolites in the urine can be found after some time after the start of therapy. The levels could be very very low so probably LC-MS/MS with high sensitivity should be used. Maybe if those concentrations are too low some blood biochemistry related to liver function could be enough? If you have a representative group of patients then it's some idea for scientific research.
Best regards
Tomasz
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