2-chloroacetamide

Endpoint summary

Additional information

Two key case studies were described in which Chloroacetamide was determined to be a skin sensitiser: 1) a pensioner using skin cleanser developed inflammatory reddening and swelling of the skin of the face, neck, nape and neck-line, on the back of hands and forearms ascending to the middle of the upper arms: a patch test containing facial cleanser was positive; 2)a worker in contact with wet cork developed an eczematous reaction on the fingers of the right hand, which improved during periods of time off and deteriorated after returning to work (Klaschka, 1975).

In a key clinical study, 296 patients with presumed contact allergy were treated with 0.1 mL of a 0.2 % aqueous Chloroacetamide solution on the back skin under occlusion for 24h (Schulz, 1984). Examination of the test areas at 24 h, 2 & 3 days after application showed positive skin reactions in 7/296 patients due to previous contact with Chloroacetamide. This complies with a frequency of 0.3 -2.8% individuals with acquired contact allergies to Chloroacetamide in the patients groups treated at dermatology departments (BG Chemie, Germany, Toxicological Evaluations no. 8 Chloroacetamide, 2000-06).

Supporting information on sensitisation potential was available from various clinical studies in which previous Chloroacetamide exposure was expected:
-Among 3254 patients tested with Chloroacetamide (0.1% in pet.), 10 (0.3%) showed a positive test reaction (Ägren et al., 1980).
-Among 104 patients with static dermatitis of the lower limbs, 3 (3%) developed a positive patch test to treatment of 1% Chloroacetamide in vaseline (Angelini et al., 1975).
-Epidermal tests with 2% Chloroacetamide m/m solution in patients allergic to woolwax showed that 18/51 (35.3%) patients reacted positive on Chloroacetamide solution (Auth et al., 1984).
-A 46-year-old healthy woman with itchy, burning swelling on eyelids showed positive reactions in a human patch test with 0.2 % pet. Chloroacetamide and non-human placental protein 10% and 30% in a human patch test (De Groot & Weyland, 1986).
-Human patch testing in patients suspected of dermatitis showed 3/501 cases (0.6%) positive to Chloroacetamide (De Groot et al., 1986).
-In an epicutaneous test on the back of patients with eczema and suspected of allergic contact dermatitis, Chloroacetamide was tested positive in 1 /ca. 200 (0.5 %) patients (Hannuksela et al., 1976).
-Chloroacetamide tested at a concentration of 0.1 % in petrolatum on 180 house painters who had a skin disease at the time of testing, showed 5 (2.8%) that had a positive reaction to the Chloroacetamide (Högberg & Wahlberg, 1980; Wahlberg et al., 1978).
-A modified Draize test with Chloroacetamide in 147 volunteers showed positive reactions in 19/33 of the females (58%) and 28/114 of the males (5 %) (Jordan & King, 1977).
-A Draize test with 1.25% Chloroacetamide in a creambase on 205 male revealed 35 with positive reactions, a sensitisation rate of 17%. Marzulli & Maibach, 1973)
-Six subjects 6 months earlier reported positive to 1% Chloroacetamide patch test, were retested in a modified Draize test at 0.05, 0.1, 0.05, and 2% applied to the upper back: 4/6 were positive at 2% and 1/6 was positive at 0.5% (Marzulli & Maibach, 1976).
- Of 81 women who had become sensitive to formaldehyde, 5% also developed an allergy to Chloroacetamide; in males this was 9% of 34 formaldehyde allergics investigated. Data for individuals who were not sensitive to formaldehyde gave markedly lower frequencies (1% and 1% among 11630 women and 6389 men), therefore findings were considered as "exposure- induced combined allergies" (Schnuch & Geier, 1997).
-Chloroacetamide was patch-tested positive for 189/16,191 dermatological patients (=1.2%); from these findings, 106 (0.7%) were very slight irritations '+' , 46 (0.3%) were doubtful (Schnuch, 1996).
-5/64 patients (7.8%) with occupational hand dermatitis (metal workers) were patch-tested positive for Chloroacetamide (Shah et al., 1996).
-Patch testing in 36 hairdressers with hand eczemas were most frequently sensibilised by glyceryl monothioglycolate (61%), p-phenylendiamine (38%), nickel sulfate (33%). 1/36 (2.7%) hairdressers tested positive for Chloroacetamide (0.2%). Any occupational related sensibilisation could not be clearly established Özkaya-Bayazit et al., 1997).
-A 27 -year old woodcutter with acute dermatitis of the dorsa and the soles of the feet reacted positive by patch testing with Chloroacetamide 0.2% pet; the impregnation shoeleather was considered to be the reason (Jelen et al., 1989).
-The frequency of Chloroacetamide-induced contact allergy tested in individuals with pre-existing lesions and suspected of allergic contact dermatitis, showed 17/5202 (0.3%) positive reactions by means of patch testing (Broeckx et al., 1987).
-In another study, the frequency of Chloroacetamide-induced contact allergy tested in individuals with pre-existing lesions and suspected of allergic contact dermatitis, showed 30/1832 (1.6%)positive reactions by means of patch testing (COLPIPA, 1987).
-Finally, a study for Chloroacetamide-induced contact allergy tested in individuals with pre-existing lesions and suspected of allergic contact dermatitis showed 20/ 8521(0.25%) positive reactions by means of patch testing (Goossens et al., 1997).

Supporting information was also available from commercial products containing Chloroacetamide or similar products (read across):

-In a 1.5 year period, 15 patients were seen with an allergic reaction to an ointment used in the treatment of chronic venous insufficiency of the legs. Subsequently, 100 patients with this disturbance were tested for their sensitivity to the ointment. The ointment contained preservative CA 24, a mixture of 70% Chloroacetamide and 30 % sodium benzoate. The preservative concentration was 0.2%, corresponding to a Chloroacetamide concentration of 0.14 %. In the study, 12 of the 100 patients tested had an allergic reaction to the ointment.As a control, patch tests were performed on 125 patients who were not known to be under treatment with the ointment. One of the 125 had a positive reaction, and this patient had been treated previously with the ointment for an ulcer of the leg. The 27 patients with known ointment allergy were tested with several of the components of the ointment. In the 22 patients tested with preservative CA 24 in a 0.2% aqueous solution, 17 had a positive reaction. Chloroacetamide, 0.2% in aqueous solution, was tested in 19 patients, and 17 had positive reactions.The authors speculated that sensitisation to Chloroacetamide might occur more easily when it is applied to broken skin and concluded that Chloroacetamide shouId be omitted from products destined for the treatment of skin diseases. (Smeenk & Prins, 1972)
-A study with 215 patients and 10 healthy persons dermally treated with a 0.1% solution of Konservierungsmittel CA 24, containing 70% Chloroacetamide and 30% sodium benozate, was free of side-effects (Röckl, 1970).
-From 736 patients suspected of having occupational contact dermatitis, occupational allergic contact dermatitis was observed in 2 patients after treatment with Euxyl K 400 0.5% pet (Aalto-Korte et al., 1996).
-Acquired contact dermatitis was documented in various cases due to products containing Chloroacetamide (n-hydroxymehylchloacetamide in Grotan HD2, Parmetal K50, Preventol D3) (Andersen & Rycroft, 1991).
-Two case studies with history of dermatitis were described with occupational exposure to glue containing Chloroacetamide 0.1 % and formaldehyde 2%. Both patients showed a positive reaction to dermal exposure (Bang et al., 1976).
-A 25-year-old woman with itching erythema and vesicles in the perioral area and on both ears was subjected to a patch test with herpes medications R Lomaherpan and R Viru Merz-Serol, showing a positive reaction to the constituent Chloroacetamide 0.07% (Detmar & Agathos, 1988).
-A 27-year-old female secretary with a history of contact allergic reactions to iodine dervatives and eczema at the fingertips showed a positive patch test to glue containing Chloroacetamide as a preservative agent.
-A 50-year-old worker, employed in a factory producing modelling plasticine (Didò) for small children reacted positively in a patch test to Preventol D5, a preservative in the plasticine containing N-methylochloracetamide (Farli et al., 1987).
-A 19 year old worker with hand eczema of 1-year duration was tested positive in a patch test with N-methylol-Chloroacetamide + O-formal of benzyl alcohol ( R Parmetol K 50) (Hjorth, 1979)
-A 48-year-old male fork lift driver working with paints with history of hand eczema showed positive reaction to a patch test with Chloroacetamide (0.2% pet.) (Jones & Kennedy, 1988).
-A 40 -year-old woman with 6-month history of a recurrent pruritic facial dermatitis showed a positive reaction in a patch test with aerosol spray astringent, Atomiseur tillel, containing Chloroacetamide and to Chloroacetamide (0.2% in pet.) (Koch, 1985)
-Chloroacetamide (2% in Trolab) was used in a patch test in 51 patients, of which 1 occupational 34 +-year old worker who had been working with cutting oils was positive (Lama et al, 1986).

-Chloroacetamide 0.1% in pet. patch tested on dermatological patients showed 7/465 of subjects positive (1.5%), of which 5 were younger women who had mainly facial lesions, most probably due to cosmetics (Meynadier et al., 1982)
-Of 18 subjects patch test tested with components of cosmetic cream, 2 showed positive for the Konservierungsmittel C, containing 70% active ingredient (Nater, 1971).
-A patient with lip inflammation after toothpaste use was found positive in a patch test with Chloroacetamide 0.2% aq (Ophaswongse & Maibach, 1995).
-A patch test performed on 3 persons 3 years after having caught a nitrile-allergy was negative for Chloroacetamide 0.5% in acetone (Richter & Scholz, 1971).
-A 30-year-old man with acute dermatitis of the back of his hands after use of a cosmetic hand lotion showed a strong positive result with patch testing to the lotion and to Chloroacetamide 0.20% in water and in pet; negative results were obtained with sodium benzoate solutions (Suhonen, 1983).
-A 55-year-old woman with severe bilateral axillary dermatitis reacted positive to patch testing with 0.2% Chloroacetamide in petrolatum; her dermatitis was attributed to her roll-on deodorant, which contained Chloroacetamide in combination with sodium-benzoate at a concentration of 0.05% (Taran & Delaney, 1997).
-A 51-year-old man with suspected contact dermatitis on forearm reacted positive to patch testing with R Euceta-Gel ointment and Chloroacetamide 0.001 %; the reaction was considered to be due to the ointment (Wantke et al., 1993).
-A 33-year-old woman with acute dermatitis of the face, occurring 1 day after painting, reacted positive to patch testing with Chloroacetamide 0.1% pet. and methylolChloroacetamide, substances present in Umwelt-Raumfarbe (Finkbeiner & Kleinhans, 1994).
-A 71 -year old man with redness, swelling and scaling of the border of the lips,reacted positive by patch testing to Chloroacetamide 0.2% aq; this reaction was considered to be due to Chloroacetamide in toothpaste (Saino & Kanerva, 1995; Machackova & Smid, 1991).
-A 55 -year old women with dermatitis in the neck region after use of hair dyes, reacted positive to Patch testing with Chloroacetamide; the reaction was considered to be due to the hair dye (Assier-Bonnet & Revuz, 1999).
-A 36 -year old male carpenter with dermatitis of the palm and fingertips, reacted positive in a patch test with Chloroacetamide 0.2% pet.; the reaction was considered to be due to Chloroacetamide in wallpaper glue (Pereira et al., 1999).