Butyl 2,3-epoxypropyl ether

Endpoint summary

Description of key information

The test substance was found to be positive in patch testing in some patients in surveys in dermatological clinics. In a human maximisation test according to Kligman in volunteers in a prison, 19 of 24 were sensitised by the test substance.

Additional information

The Maximization Test was performed according to the method of Kligman (1966) in a panel of 25 healthy adult subjects (volunteering inmates from Holmesburg Prison). To do so, sensitizing patches were applied to an extremity, either the forearm or the lower leg in the calf region. The entire series of patches was applied to exactly the same site. 1.0 mL of 5% aqueous sodium lauryl sulphate (SLS) to a 1.5" square of Webril was delivered fastened occlusively to an extremity for 24 hours. This treatment produced a moderate inflammatory reaction. To the same site a 48 hour occlusive patch was applied with the test material (10 %). This sequence of alternating 24 hour irritant and 48 hour allergen patches was repeated for a total of five exposures. The procedure therefore consisted of five 48 hour exposures, each one preceded by a 24 hour pre-treatment with 5% SLS. The SLS pre-treatments were eliminated if at any time the skin became too inflamed. The aim was to keep the skin moderately inflamed during the exposures. The provocative test consisted of pre-treating the skin occlusively with 0.4 mL of 10% SLS on a 1.0" Webril square for 1 hour. This produced sub-clinical inflammation in 48 hours. For the test substance a 10% solution was applied. Irritancy was established by pilot testing of no less than 10 subjects. The challenge reaction was read immediately after removal of the 48 hour patch and again in another two days. Subjects were asked to return if reactions developed still later. An evident erythema was considered the minimum positive response. Marginal erythematous reactions were operated one week later. A control patch was necessary for the provocative test consisting of petrolatum applied for 48 hours to a site pre-treated for one hour with 10% aqueous sodium lauryl sulphate. The control site usually showed no reaction, or occasionally a very mild erythema may be present. The allergen treated site is not regarded as positive unless it is clearly more inflammatory than the control site. Nineteen out of 24 subjects were found to be sensitized to the test substance.

In an published article comparing several skin sensitisation tests, the test substance was also noted as positive in the Human Maximization test.

In a published study with patients with suspected occupational skin disease were patch-tested with a modified European standard series, other relevant series related to their work or hobbies and their own substances (Kanerva et al, 1999). Patients with exposure to plastics and glues were often patch-tested with a plastics and glues series comprising the test substance. The article reports of 6-year patch-test results with these allergens. In this study, the test substance (0.25 % w/w) was tested in 310 patients (1991-1996) of which 2 were tested positive for an allergic reaction (0.6 %).

In a earlier compilation of 3-year statistics (instead of 6) on patch testing with plastic and glue allergens, 145 patients were patch tested with the test substance (Kanerva et al, 1997). Most patients were referred because of suspected occupational dermatoses. Patients were patch tested with a modified European standard series, and their own substances. Those with exposure to plastics and glues were usually patch tested with our plastics and glues series including the test substance (0.25% in pet.). Patch testing was performed with 2 days occlusion and 3 readings (usually on D 2, 3 and 4-6). Allergic reactions were scored according to ICDRG recommendations, +, ++ and +++ reactions being considered allergic. Irritant reactions were also recorded. Reactions scored as doubtful (?+) or irritant (IR) were classified as irritant. Of the 145 patients tested to the test substance 1 showed a positive allergic reaction (0.7%).

In a published article 839 patients were patch tested with a series of 31 plastics and glues allergens at a dermatologic clinic over a period of 7 years (Tarvainen, 1995). The test substance specifically was tested in 343 individuals. Regarding the test substance. Of the 343 patients tested with the substance, none of them showed an allergic reaction.

In a published article regarding an epoxy resin manufacturing plant, 26 of 228 (11.4%) workers had work-related eruptions; 19 were patch tested (Prens et al, 1986). The test series consisted of chemicals used in the manufacturing process, a standard battery and some other sensitizers. For each worker, the time between the first exposure to the chemicals in the plant and the development of lesions was calculated and designated as the "latency period". Non-irritant concentrations of most of the chemicals used in the production process were determined based on available data. For the test substance of interest this was 0.25 and 0.5 % in MEK. The ICDRG Standard Series, including formaldehyde, fragrance-mix and an epoxy resin, and certain other common sensitizers (among which the test substance) were tested simultaneously in the 19 participating workers. All workers were patch tested during the same week. The test-results were graded as follows: - = negative (no reaction or a dubious reaction (only slight erythema)); + = positive (erythema, mild edema); ++ = positive (erythema, edema and papules); +++ = strong positive (erythema, induration, papules, vesicles); ++++ =extremely positive (erythema, induration, bullae exceeding the border of the test area). A positive test was found in only 1 case to the test substance of interest, with a latency of 8 weeks.

Finally, 20 patients with contact allergy to epoxy resins were tested with the commonest reactive diluents, namely phenyl glycidyl ether, butyl- and allyl glycidyl ether (Fregert and Rorsman, 1964). Of 20 patients, 14 were found to react to phenyl glycidyl ether, 3 to butyl- and 2 to allylglycidyl ether (0.25% in acetone). Four patients who reacted to phenyl glycidyl ether were also tested and found to react positively to the closely related cresyl glycidyl ether.