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Table 4 Summary of general and reproductive effects of PTMC products

From: Toxicology and teratology of the active ingredients of professional therapy MuscleCare products during pregnancy and lactation: a systematic review

Ingredient Species General toxicology Reproductive effects References
Methylsulfonylmethane Human • Topically, there are no adverse reactions. • Till date, no data. [11-16]
• There are no studies on long-term use.  
Animal • Orally, it has low toxicity. • Do not induce structural or fetal anomalies.
• Long-term use did not cause adverse events.  
Camphor Human • Topically, poisonings were reported in children and adults. • Topically, the frequency of birth defects was less. [17-28]
• Orally, it caused fatal symptoms in children. • Orally, cross the human placenta, however, till date, there are no adverse fetal effects.
Animal • The oral LD50 = 1.3 g/kg in mice. • Orally, there are no congenital abnormalities in rats and rabbit.
Menthol Human • Topically, it is safe. • Till date, no data. [29-31]
Animal • Topically, acute dermal toxicity was reported with LD50 = 5 g/kg in rabbit. • There is no teratogenic effect in mice, rats, hamsters, or rabbits.
• Orally, toxicity was reported at LD50 = 2.9 g/kg and 3.1 g/kg in rat and mice, respectively.  
Wintergreen Oil Human • In cosmetics, methyl salicylate is safe, however, might cause local necrosis. • Till date, no data. [32-42]
• There are some reports for tinnitus, diplopia, shortness of breath, and respiratory alkalosis.  
Animal • Topically, sub-chronic exposure might lead to kidney damage in rats. • It is associated with increased risk of abnormalities.
Glucosamine Sulfate Human • Topically, it did not cause toxicity or adverse effects. • There is no increase in risk of malformations. [43-47]
Animal • Topically, it is considered safe. • Teratogenic effects were not reported in mice or rabbits exposed to glucosamine.
Sodium Chondroitin Sulfate Human • Topically, there are no adverse events. • Till date, no data [43,48-52]
• It interferes with progression of osteoarthritis.  
Animal • The oral LD50 for mice is greater than 10 g/kg. • There is increased risk of cleft palate and tail abnormalities in mice.
  • Orally, there are no adverse effects in mice and rabbits.
Eucalyptus Leaf Oil) Human • Topically, it is safe. • Till date, no data. [53-56]
• A report of fever and seizure-like motor activity -in slurred speech, ataxia, and muscle weakness were reported in children.  
• Orally, there are minor side effects.  
Animal The oral LD50 = 2.5 g/kg in rats. • There are no adverse outcomes in mice.
Grape Seed Oil Human • Topically, it is safe. • Till date, no data. [57-60]
Animal • There are no safety issues associated with acute and chronic safety studies rats • The grape seed extract was non-mutagenic in mice.
  • Several reports showed that LD50 for dermal application is greater than 2 g/kg in rats.
Vitamine E Human • Topically, it is safe. • There are no risks of stillbirth, perinatal death, preterm birth, intrauterine growth restriction, or mean birth weight. [61-66]
  • High doses were associated with reduction in birth weight.
Animal • Topically, it is safe. • Malformation was not greater than expected in offspring of rats and mice. [67-71]
Thymol Human • Topically, it is safe. • It is not associated with increased risks of birth defects. [21,72-76]
• It is toxic to mucous membranes and to kidneys, liver, and central nervous system.  
Animal • Topically, it is safe. • Might cause adverse reproductive effects.
Sea Cucumber Extract Human • Topically, it is safe • Till date, no data. [77-81]
Animal • Topically, it is safe. • Till date, no data.
Aloe Barbadensis Leaf Juice Human • Topically, it is safe, however, not recommended for children under age of 12 years. • Orally, it is not recommended in pregnancy or lactation. [82-88]
• Orally, there are adverse effects in rare cases.  
Animal • Topically, it is safe. • Teratogenic effects have been reported with high oral doses in rats.
Peppermint Oil Human • Topically, it caused skin irritation with frequent use of oil. • It induces menstruation and, thus, it is not recommended at high oral doses during pregnancy. [83,89-91]
• Orally, enteric-coated capsules were not associated with adverse reactions. • There is insufficient evidence to determine the safety of peppermint oil during lactation.
Animal • The oral LD50 was reported at 2490 mg/kg in mice and at 2426 mg/kg in rats. • Orally, the LD50 was 2490 mg/kg in mice and 2426 mg/kg in rats.
  • The peppermint oil was used to induce menstruation and it is not recommended at high oral doses in pregnancy.
Boswelli, and Magnesium chloride Human • Topically, boswelli is associated with dermatitis. • Orally, there is lack of evidence on safe use of boswelli during pregnancy and lactation. [92-99]
• Orally, boswelli is associated with gastrointestinal effects including, nausea, abdominal fullness, and epigastria. • Similarly, magnesium chloride studies failed to demonstrate risks of birth defects to the fetus.
• Orally, magnesium chloride is not recommended for patients with renal impairment.  
• Both magnesium and ilex are safe for topical use.  
Animal • Topically, boswelli is safe in mice, rats and monkeys. • There is lack of evidence on safe use during pregnancy and lactation.
• Orally, boswelli was not associated with mortality in rat and mice.  
• In rat and monkey, there was no change in behavior, clinical, biochemical, or pathological data when boswelli was used orally.