resorcinol; 1,3-benzenediol

Endpoint summary

Description of key information

Acute effects from various human experience regardless of reliability are presented.

Additional information

Toxicokinetics, Metabolism and Distribution

Humans

In vitro permeability studies using human skin treated with 10% w/v resorcinol, reported there was a long lag time (80 min) (Roberts et al., 1977). A steady state permeability coefficient (Kp) of 0.00024 cm/h was calculated.

In a human volunteer study to measure absorption and metabolic disposition, 2% resorcinol (800 mg resorcinol/day, a maximal exaggerated use level) was applied topically in a hydro-alcoholic vehicle over an application area of 2600 cm2 twice a day, six days a week for four weeks to three male volunteers with one control volunteer (Yeung et al., 1983). The test substance penetrated the skin at a rate of 0.37 μg/cm2/hour. After two weeks of application, an average of 1.64% of the dose was being excreted in 24-hr urine specimens as the glucuronide or as the sulfate conjugate. There was no resorcinol or its conjugates in blood drawn at week 1, 2, 3, and 4.

In one female patient with leg ulcers treated dermally for 13 years with ca. 500g/week of an ointment containing 12.5 % resorcinol, 2.1 % of the applied dose was found in urine as glucuronide and monosulphate metabolites (Thomas and Gisburn, 1961).

Humans

Acute effects:

Following accidental oral ingestion of resorcinol (50 g) to a 27 yr old pregnant female (at 30 weeks of pregnancy) major clinical findings were: unconsciousness, drowsiness, and respiratory failure that required mechanical ventilation along with tonic-clonic seizures and hypothermia (Duran et al., 2004). In addition, the laboratory findings were leucocytosis, high bilirubin levels, severe metabolic acidosis and green-colored urine. The foetus was considered dead at 24 h after delivery. The mother’s recovered with supportive management. Basic approach to the patient with resorcinol poisoning should include the initial stabilization of immediate life-threatening problems and elimination of the toxin. 

In humans, the following symptoms of systemic intoxication are reported after dermal application of excessive doses of resorcinol to open or abraded skin: dyspnoea, tachycardia, cramps, liver and kidney damage, methemoglobin formation, hemolysis, cyanosis, hemolytic anemia, haemoglobinuria, hypothyroidism and local ochronosis and myxoedema (Becker, 1933; Berthezene et al., 1973; Bull, 1950; Cunningham, 1956; Garton, 1949; Guinet, 1967; Haenelt, 1925; Kalkoff, 1962; Katin et al., 1977; Luepke, 1979; Murray, 1926; Nothen, 1908; Thomas, 1961; and Wuethrich et al., 1970).  For babies and infants, dermal application of resorcinol can prove fatal when applied excessively.

Collectively these signs of toxicity in adults and children are rarely observed and confined to a period of time when resorcinol was utilised at high concentrations (up to 50%) and was applied to open wounds.

It is important to note that over application of dermatological preparations and creams was a problem in the early 20^th century (EC, 2002).  These instances represent exaggerated usage conditions and are not considered of clinical relevance to humans under current practices and conditions of current uses. Since the 1950’s the regulation of resorcinol-containing topical ointments, the concentration of resorcinol has lowered to no more than 5% together with greater supervision by the prescribing professional where applicable and clearer product information. 

For the past thirty years topically applied resorcinol-containing applications, representing a significant number of years of patient and consumer years of exposure, have been demonstrated to be well tolerated when used within the limits of the Cosmetic Ingredient Review and as an approved acne ingredient up to 2% in combination with sulphur (US. Food and Drug Administration (FDA) 21 Section 310.545, Section 333.310; Section 333.320).

Data from human usage over the past 30 years has not shown thyroid effects in humans at therapeutic doses or industrial concentrations. 

Humans

Sensitisation:

Data are available regarding experience in human dermatitis/allergy clinical cases. Resorcinol is considered a moderately potent sensitiser,within the local lymph node assay but this does not correlate with a high incidence of reports in humans (Broeckx et al., 1987; Sosted et al., 2013; CIR 1986). When considering the extensive use of resorcinol, the human data suggest resorcinol is an uncommon/rare sensitiser.

On patch-testing, resorcinol elicited allergic skin reactions in 0.7-0.8% of 1694 dermatitis patients. In case histories of 34 dermatitis patients, resorcinol was established as the cause of allergic skin reactions after epicutaneous testing (Baer et al., 1995; Bandmann, 1966; Eiermann et al., 1982; Howell, 1946). In 42 workers from a tyre factory exhibiting hand dermatitis, an epicutaneous test with resorcinol performed in accordance with ICDRG proved negative (Abbate et al., 1989). When patch tested with resorcinol (2% in petrolatum), 4 of 302 hairdressers suffering from contact dermatitis gave a positive reaction. No further details are available (Guerra et al., 1992). In one patient who developed contact dermatitis after application of Castellani paint to the skin, application of resorcinol (5% in petrolatum; ingredient of the paint) yielded a positive patch test after 48 hours (Marks, 1978). Three female acne patients suffering from contact dermatitis gave a positive patch test for resorcinol (2% in petrolatum) after 48 and 72 hours (Serrano et al., 1992). In a study of 1187 subjects tested over a 25 -year period, following European Society of Contact Dermititis guidelines, five positive patch test reactions were observed, corresponding to a rate of 0.42% (Darcis and Goossens, 2016). Positive patch tests for resorcinol (tested at 2%) were reported in hairdressers (tested at 2%) and hairdressers' clients (test concentration not stated). With respect to hairdressers, two of the six centres reported positive patch tests ranged from 0 to 2.8%. With respect to hairdressers' clients, four centres reported patch test results, with only one site reporting a positive patch test (1.9%) (Frosch et al., 1993). A similar review from dermatology centres collected patch test data over a 2 -6 year period with resorcinol tested at 1%. Two positive results were reported from 501 patch tested, corresponding to a rate of 0.4% (Katugampola et al., 2005). Patch tests with 399 hairdressers with resorcinol (tested at 1%) applied to the upper back under occlusion for 48 hours resulted in only one positive patch test, corresponding to a rate of 0.4% (Schwensen et al., 2013). In a study of 2939 eczema patients, resorcinol (tested at 1%) provided a positive response in three patients, corresponding to a rate of 0.1% (Sosted et al., 2013). However, no evidence of sensitisation was observed in patch tests conducted in 196 individuals in Japan at 1% resorcinol (Ito et al., 2017).

Human

Thyroid: See information on specific investigations.