Dosing and Toxicity of Thymus vulgaris

 Specific dosage of thyme has limited scientific evidence support. It is not clear that  how the efficacy and safety is balanced in optimal doses of natural products. It is not clear that what are the active components of the product, standardization may not possible, clinical effects of different brands due to preparation of the products may vary from manufacturer to manufacturer. Volatile oil is about 0.4% to 3.4% in common thyme but after standardization of extract contain 0.6% to 1.2%. These standardization of thyme found in commercial products such as topical cosmetic formulations or mouthwash(Manou et.al, 1998). In treatment of actinomycosis, onycholysis (Seperation or loosening of fingernail or toenail) and paronychia ( inflammatory tissue surrounding fingarnails) experts having recommended use of thymol. In little amount of thyme present in food is safe to consume but in orally it’s not exceed10g because 10g dried leaf contain 0.03% phenol and non diluted form of thyme oil is unsafe to use.

Oral recommended dosage:

General dosage for an adult (Above 18 year): one to two grams of thyme extract taken daily

Oil: Thyme oil is consider to be highly toxic, two to three drops of thyme oil on the sugar cube 2-3 times daily has been used.

Liquid extract: 20-40 drops liquid extract (1:1 weight/volume fresh leaf or 1:4 dried leaf) three times daily in juice; or 40 drops tincture (1:10 in 70% ethanol) up to three times daily for upper respiratory tract infection. Safety and efficacy have not been proven.

Tea: it has been recommended to steep 1-2 grams of dried herb in 150 mL boiling water for 10 minutes, strain, and drink several times daily for upper respiratory tract infection/bronchitis symptoms.

Mouthwash: Thymol is a constituent in some combination mouthwash products such as Listerine (demonstrated to be efficacious in the reduction of oral bacteria). For periodontal prophylaxis, it has been recommended to steep 5 grams dried leaf per 100 mL boiling water for 10 minutes and strain (5% infusion).

 

Topical

 

 oil/ointment: For alopecia areata, 2-3 drops of an essential oil combination (thyme, lavender, rosemary, and cedarwood added to grapeseed and jojoba oil) massaged into the scalp every night for seven months has been studied (Hay IC, et.al.1998). For paronychia, 1 drop of 1-2% thymol in chloroform to the affected area three times daily, or 1 drop of 4% thymol in chloroform to a chronically affected area three times daily has been used (Wilson JW et.al, 1965)

 

For childrens doctors not prescribed use of thyme medicines. Avoid hypersensitivity patients from thyme medicines. Symptoms of allergy may include nausea, vomiting, runny nose, severe itching, swelling under the skin, difficulty swallowing, altered voice, low blood pressure, contact dermatitis, inflammation of lung cells, and progressive respiratory difficulty. Occupational asthma has been reported in hypersensitivity patients.

 

 

 

 

 

 

TOXICOLOGY

            Thyme oil contain high amount of thymol and carvacrol that can be highly toxic to the childrens. If it uses in high dosage it shows allergic reactions. It can be neurotoxic. It has been suggested not to exceed oral doses of 10 grams of dried leaf with 0.03% phenol (calculated as thymol) per day to prevent toxicity. Signs of toxicity include nausea, and based on animal studies may include tachypnea and hypotension. Oil extraction of thyme oil is considered to be highly toxic (Kagramanov KM et.al, 1997)

 

Precautions:

Allergy:

Avoid use of thyme medicines  to members of the Allergic patients. Thyme is belonging to the lamiacea (mint) family cause nausea, emesis, pruritis, angioedema, dysphagia, dysphonia, hypotension, and progressive respiratory difficulty.

Adverse Effects:

General: Thyme oil should not be taken orally and should be diluted for topical administration due to potential toxic effects.

Neurologic/CNS: Headache and dizziness have been associated with oral ingestion of thyme and thyme oil. Oral ingestion of thyme oil may cause seizure and coma.

Ocular/Otic: Conjunctivitis has been reported in a farmer exposed to thyme dust.

Dermatologic:Dermatitis caused by thyme dust in farmers exposed to dried thyme. Allergic contact dermatitis was reported in a 70-year-old woman six weeks after initiation of 4% thymol once daily to a chronic paronychia. Topical application of Listerine antiseptic solution to a chronic parenchyma of the toe by a 43-year-old man resulted in contact dermatitis. As an ingredient in toothpaste, cases of inflamed lips and tongue have anecdotally been attributed to thyme oil.

Pulmonary/Respiratory:.High doses of thyme or thyme oil have elicited tachypnea in animals. Oral ingestion of thyme oil may lead to respiratory arrest (anecdotal). Cardiovascular: Hypotension after ingestion of thyme seasoning was seen in a 45-year-old man, possibly related to an allergic response. Animal studies have reported both hypotension and increased cardiac contractility. Anecdotal reports suggest that bradycardia may be associated with ingestion of thyme, and cardiac arrest may occur with oral intake of thyme oil.

Gastrointestinal: Oral thyme and thyme oil may elicit heart burn, nausea, vomiting, diarrhea, and gastrointestinal irritation (anecdotal).

Endocrine: An extract of Thymus serpyllum, a related species to Thymus vulgaris, has been shown to exert anti-thyrotropic effects in rats, causing decline in thyroid stimulating hormone and prolactin. Estradiol and progesterone receptor-binding activity has been demonstrated in vivo. Endocrine effects of Thymus vulgaris in humans are unclear.

Genitourinary: Oral thyme has anecdotally been reported to exacerbate inflammation associated with urinary tract infections.

Musculoskeletal: Oral use of thyme or thyme oil has been associated with muscle weakness in anecdotal reports, although details are limited.

 

 

 

 

 

 

 

 

Precautions/Warnings/Contraindications:

·         Avoid contact of allergy/hypersensitivity to members of the Lamiaceae (mint) family or to any component of thyme.

·         Avoid oral ingestion or non-diluted topical application of thyme oil due to potential toxicity.

·         Avoid topical preparations in areas of skin breakdown or injury, or in atopic patients, due to multiple reports of contact dermatitis.

·         Use cautiously in patients with gastrointestinal irritation or peptic ulcer disease due to anecdotal reports of gastrointestinal irritation.

·         Use cautiously in patients with thyroid disorders due to observed anti-thyrotropic effects in animal research of the related species Thymus serpyllum.

Pregnancy and Lactation:

Thyme is not recommended in pregnancy or lactation, due to lack of sufficient data. A 1975 review of plants as possible new anti-fertility agents classified thyme as an emmenagogue and abortifacient.

 

 

 

            The acute toxicity of thyme oil and its active constituent thymol are summarized in Table .

Table

Acute Toxicity of Thyme Oil and Thymol

Study		Results		Source
Acute oral toxicity		LD50 (rat): 2,840 mg/kg, mouse: 1,250mg/kg, rabbit: >5000mg/kg Thymol: LD50: (rat) 980 mg/kg bw, (mouse) 1050-2000 mg/kg bw, (guinea pig) 880 mg/kg bw		(Gwynn 2014; HSDB 2015)
Acute dermal toxicity		Thymol: LD50 (rabbit): >5000 mg/kg		(Sigma-Aldrich 2014)
Acute inhalation			Not found
Acute eye irritation			Not found
Acute dermal irritation			Not found
Skin sensitization		Thymol: Guinea pig: No sensitization reaction		(HSDB 2015)

 

 

Other than oral toxicity, the acute toxicity of thyme and thyme oil is estimated by thymol.

 

 

 

 

 

Sub-chronic Toxicity

No data was found on the subchronic toxicity of thyme or thyme oil; the subchronic toxicity of thymol is summarized in Table .

Table

Sub-chronic Toxicity of Thymol

Study		Results			Source
Repeated Dose 28-day Oral Toxicity Study in Rodents			Not found
90 day oral toxicity in rodents			Not found
90 day oral toxicity in non-rodents		No effect			(Hagan et al. 1967)
90 Day dermal toxicity			Not found
90 Day inhalation toxicity			Not found
Reproduction/development toxicity screening test			Not found
Combined repeated dose toxicity with reproduction/de­velopment toxicity screening test			Not found
Prenatal developmental   toxicity study		Possible teratogen			(Verrett et al. 1980)
Reproduction and fertility effects			Not found

 

A 19 week subchronic toxicity study performed on Osborne-Mendel rats determined thymol to have a no– observable-effect level of 1,000 mg/kg of body weight (Hagan et al. 1967). Thymol caused developmental abnormalities in chicken embryos, but the effects were not significant enough to classify it as a known teratogen (Verrett et al. 1980). However, thymol exhibited genotoxic and potent mutagenic activity against Drosophila melanogaster fruit flies (Karpouhtsis et al. 1998)

Chronic Toxicity

No studies on the chronic toxicity of thyme or thyme oil were found. The chronic toxicity of thymol is summarized in Table 4.

.

Study	Results	Source
Chronic toxicity	Ames test: Mildly positive to negative.	(Stammati et al. 1999; Azizan and Blevins 1995)
Carcinogenicity	Negative	(Andersen 2005; Stoner et al. 1973)
Combined chronic toxicity & carcinogenicity	Not Found

Thymol (1.2 and 6.0 g/kg) was negative for promoting lung tumors in mice (Stoner et al. 1973). Anti-tumor effects were observed for thymol (Andersen 2005).