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• Salicylate is a family of chemical substance which have analgesic and anti-inflammatory effect. The most known is Aspirin which is acetylsalicylic acid and is used also as pain killer. Ingesting a high dose of it can cause death. However, methyl salicylate is much more toxic than acetylsalicylate acid. A 10kg child can develop life threatening poisoning with the ingestion of a small sip of preparation of methyl salicylate [172]. There are different creams and herbal oils that contain salicylate and the percentage of the salicylate out of the total product ranges usually between 1 and 15% but in some products, it can reach 30 % [177].

       Even though absorption of methyl salicylate by the skin is relatively low, and its plasma concentration is low [30], rubbing                   regularly cream containing methyl salicylate on the skin has a high toxic effect and the most sensitive groups to be affected by         it are children and old people [173]. Regular application of cream against muscle pain or arthritis while heating the skin with                heating pad resulted in death cells in the muscle and inflammation of the kidney [174]. 

       In a mild to moderate toxicity, methyl salicylate produces reversible tinnitus (perception of noise or ringing in the ears) in                   animals and humans as well. It has been shown that systemic application of salicylate changes the spontaneous neuronal                 activity (neural activity that is not driven by an external stimulus) in several parts of the auditory pathway [33]. In severe                       intoxications, conditions such as encephalopathy, coma, seizures, and cerebral edema may be seen. Cerebral dysfunction                 may include symptoms ranging from confusion to coma [176]. An 80 years old woman showed symptoms of confusion after 6           days of application of a topical salicylate preparation on the skin. The cream penetrated the skin and move with the blood                 stream, passed the Blood Brain Barrier and entered the brain [175].

• Eucalyptus globulus leaves oil is often present in an ointment or gel as a topical treatment for muscle, joint pain and acne. It can be very poisonous if it is taken orally, and it can affect the central nervous system. It would result in loss of reflex, loss of consciousness and possible progression into a coma. It should not be used as an ointment on the face or nose of children. [34].

• Pinus pumilio oil - Not enough is known about the use of the dwarf pine needle oil during pregnancy and breast-feeding, therefore, not enough is known about its effect on the development of the embryo.

       Both Eucalyptus globulus and Pinus pumilio oils are used to massage the body and are absorbed by the skin.

• Petroleum has an effect on brain function leading to a neurasthenia (weakness of nerves) and a dementia (decline in memory or other thinking skills) [35]. However, it does not penetrate through the skin into the body [36].

• Paraffin (Kerosene) can cause hypoxia (deficiency in the amount of oxygen reaching the tissues) in the brain [37]. However, it does not penetrate through the skin into the body [36].

• Colour Cl47000 (disodium salt of disulphonic acid) is not recommended for use by children. It is banned in Australia, Japan, Norway and the United States [38]. It is absorbed by the skin and can cause irritation.

• Colour Cl26100 (disazo color- 1-(4-(Phenylazo) phenylazo)-2-naphthol) is restricted for use in Canada as it is expected to be toxic or harmful due to its persistent, bio-accumulative presence in wildlife. It is absorbed through the skin completely (100%) [39].

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The possible effects of Robb ointment on the development of the brain of a baby.

Ointments like Robb are applied to the head of a baby every morning and evening for as long as two years.

Robb ointment is meant to be used for the relief of symptoms of cold and muscle pain.

Some chemicals in the ointment are poisonous and harmful to the brain.

Applying the ointment on a hot or warm skin increases the absorption of the chemicals through the skin, and thus the concentration in the blood serum and in the brain cells.

Short heat application (43°C for 60 seconds) was reported to cause significant cutaneous (skin) hyperthermia with up to a twofold increase in skin perfusion [92].

There are more publications on the following three chemicals in the Robb ointment than on its other ingredients regarding their adverse effects on the brain and they will be discussed here.

• Methyl salicylate:

Salicylate causes a significant increase in the concentration of serum free tryptophan and stimulates the synthesis of 5-HT in the brain. The effect of serotonin has already been discussed under the "Molecular changes under hyperthermia" page. In addition, methyl salicylate causes an oedema in the brain that leads to the destruction of nerve cells. Salicylate, which stays many hours on the skin of the baby will enhance the elevated serotonin level in the brain hours after the hot water massage to the head of the baby was ended [93]. As the amount of Salicylate accumulates and its level increases in the blood, the elimination half-life of the salicylate from the body can increase between 3 and 12 hours regularly to unpredictably 30 hours in the setting of an overdose [173]. 

A salicylate serum concentration in the blood which is bigger than 25 mg/dL (250mg/liter) or ingested dose of above 150 mg salicylate/kg of body weight are toxic levels and causes damage [173, 176].   

So how much Salicylate does a baby who pass the hot water massage and the application of the Robb ointment to his or her head have in the blood? 

A weight of a newborn baby is between 3 to 4 Kg, and the toxic dose of methyl salicylate ingested should be between 450 to 600 mg. The weight of the ointment in the Robb container (Picture1) is 32 grams, and the methyl salicylate in it is 4% or 1.28 gram, which is equal to 1280 mg. The portion that a woman rubs on the anterior fontanelle and the head of a baby is approximately 0.008 from the total quantity of the methyl salicylate which is equivalent to 10.2 mg. The mother usually puts the ointment once or twice a day. So, the baby receives a regular topical application of methyl salicylate up to 20.4 mg a day. By ingesting the same quantity of methyl salicylate, it will take around 6 to 8 weeks to reach the minimum toxicity level. By absorption of the methyl salicylate through the warm skin of the head of a baby after the hot water massage, the time to reach toxic level would be even shorter. After ingesting methyl salicylate, the toxin moves in the general blood stream of the body and therefore only some potion of the methyl salicylate would reach the brain. However, through the warm skin of the head of the baby and especially through the warm skin covering the anterior fontanelle the absorption of the methyl salicylate is very high and it would penetrate directly into the brain blood vessels and the nerve cells of the brain, thus causing wider and greater damage to the brain than if the baby was to swallow 20.4 mg methyl salicylate every day. In addition, taking in consideration that as the amount of salicylate in the blood increases gradually, it takes the body longer time to secret the methyl salicylate through the urine, thus accelerating the accumulation of the chemical in the brain. All these would increase the effect of the methyl salicylate on the changes that occur in the nerve cells of the brain and the cerebral dysfunction. 

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• Menthol:

Menthol was found to up-regulate the function of GABAa-Receptors, which is the binding site for GABA inhibitory neurotransmitter by increasing the number of these receptors [94]. GABA regulates the proliferation of neural progenitor cells, the migration and differentiation of neurons, the elongation of axons or dendrites, and the formation of synapses [95, 96, 97]

However, a high dose of menthol is needed to activate GABAa-receptors [98]. It is possible that such a high dose of menthol is reached by the regular application of the ointment every morning and evening for a long time. The amount of menthol would gradually accumulate and may reach the critical threshold for damage. Activation of GABAa-receptors causes the release of the Brain-Derived Neurotrophic Factor (BDNF), a protein growth factor. BDNF encourages the growth and the differentiation of new neurons and synapses [99, 100], and increases excitatory synaptic signaling partly through the post-synaptic suppression of GABAergic signalling [101]. Normal brain development requires a delicate balance between regulation of the inhibitor neurotransmitter GABA and the production of BDNF. Menthol changes this balance and hence disturbs normal brain development.

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If BDNF promotes growth of neurons and synapses, how harmful will it be if the menthol (that is slowly absorbed through the skin of the head of a baby and passes through the open fontanelles to the brain) increases the level of the BDNF?

A high levels of serum BDNF were found in children suffering from an Attention Deficit Hyperactivity Disorder (ADHD) [102], and a high level of BDNF was negatively correlated to intelligence [103].

Also, people who smoke mentholated cigarettes have an abnormally high level of BDNF [104].

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It is interesting to note that the regular daily consumption of some products can affect the development of our babies without us knowing it. The assessment of the impact of pre-maternal smoking on the fetal growth of African American and Caucasian births in USA, showed that the African American pregnant smokers gave birth to babies who weighed less than the babies of Caucasian smokers. 

Why this racial disparity, given that the Caucasian women tended to smoke more cigarettes during pregnancy than the African American women did?

The African American women smokers tended to smoke mentholated cigarette three times more than the Caucasian women smokers. Tobacco exposure limits the growth of the fetal brain, lungs and other essential organs. Prenatal use of tobacco impairs the cognitive ability of a child. Mentholated cigarettes increase the damage the nicotine inflicts on the brain of a baby. When Raynolds R. J., a tobacco company executive at that time, was interviewed about the effect of mentholated cigarettes the company produced, he said, “We don’t smoke this shit (mentholated cigarette), we just sell it. We reserve that right for the young, poor, black and stupid”  [105]. 

 

• Camphor:

The application of an ointment containing camphor and other terpenic oils (plant oil) on the skin of children is a common traditional practice in many parts of the world. According to the annual report of the American Association of Poison Control Centers, National Poison Data System, 11,521 cases of camphor exposure in children aged less than 5 years were reported to United States poison control centers in 2013 alone [106]. Camphor penetrates the brain and causes demyelination of axons, and it diffuses white matter in adults [107]. This reduces the speed of the neural impulse through the axon. Camphor also causes injure to neural pyramidal cells resulting in their premature death (necrotic pyramidal cells). Perivascular (around blood vessels) and perineuronal (around neurons) oedema in the brain were found in a child due to exposure to camphor [108]. These types of damage resemble the ones occur when there is destruction of the myelin sheath around the neuron in hyperthermia. 

Mothers in Cambodia reported applying ointments containing camphor and terpenic oil compounds to the skin on the abdomen and the anterior fontanelle, especially after bathing a young infant. The reason for the application of the ointment on the anterior fontanelle was to avoid cold and to help the baby breathe easily. The ointment was applied after bathing one or twice a day from one month onward after the birth [109]. This practice resembles the one in Ghana and probably originated from the same misconception regarding the anterior fontanelle. The difference is that in Ghana the ointment is applied after heating the head, which doubles the absorption of the chemical through the skin [92, 110].

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