Glyoxal

EU 1223/2009 Annex III — SCCS opinion: Opinion on Glyoxal

Acute Dose Toxicity Dermal Glyoxal (10%) had a dermal LD 50 of >5000 mg/kg in rabbits.2 In another study Glyoxal (30%) had a cutaneous LD 50 of >20 ml/kg in guinea pigs and was classified a moderately strong skin irritant. A mixture containing 1.3% Glyoxal was applied (2 g/kg body weight) to shaved and abraded skin sites on 10 albino rabbits (5/sex). The test material remained in contact with the skin for 24 h and then the skin was washed. Observations  Distributed for comment only -- do not cite or quote were made for a 2-week period. Slight erythema and edema were visible at the 2- and 4-h observations. No treatment- related lesions were found at necropsy. The LD 50 for the mixture was >2 g/kg. A 40% Glyoxal solution (2000 mg/kg) was applied in a single 24-h semiocclusive patch to clipped sites on 10 rats (5/sex). Sites were rinsed after patch removal. Erythema was noted at the application sites during the 14-day observation period. No treatment-related lesions were noted at necropsy. The LD 50 was >2000 mg/kg for the solution. A modified Draize dermal study was conducted using six female rabbits. No irritation was observed during three applications of 0.5 mL of a 40% aqueous solution of a nail enamel containing 0.5% Glyoxal made under a topical dry patch to the clipped back or side of the animal and at 24 and 48 h after application. Acute dermal studies are summarized in Table 2. The dermal LD 50 for Glyoxal was reported to be 800 mg/kg (active ingredient) in rats, 2000-12,700 mg/kg (active ingredient) in rabbits, and 5000-10,000 mg/kg (active ingredient) in guinea pigs.8 Skin necrosis, congestion and hemorrhage of the lung, and congestion of the liver and kidneys were observed in rabbits exposed to 40% Glyoxal. Oral A range of oral LD 50 values has been reported.2 The LD 50 of aqueous Glyoxal was 2.02 g/kg in male rats and 760 … [kırpıldı — bölüm toplam 21592 karakter]

Retrospective and Multicenter Studies Of 14 workers who had contact with Glyoxal (40%), 9 exhibited a contact dermatitis with localizations mainly on the lower arms and fingers.7 Patch tests with Glyoxal (20%) resulted in a positive reaction in 7 of 9 workers. In a multicenter study of dermal sensitivity, the records of 31,849 health care workers from 24 allergy departments between 1992 and 1995 were evaluated; 4.2% of the 774 female patients working in the medical profession were found to show positive reactions to patch tests of Glyoxal, whereas only 1.4% of the control group (1895 persons not in the medical profession) were found to be positive.7 In a continuation of this multicenter study, between 1997 and 1999, patients (2689) were patch tested with Glyoxal (trimer; 1% in petrolatum).7 Positive reactions were observed in 1.6% of the patients, irritation in 0.3%, and questionable (i.e., non-allergic) in 0.6%. SUMMARY OF NEW DATA In a safety assessment published in1995, the CIR Panel concluded that the data were insufficient to determine the safety of Glyoxal as used in cosmetic products. In an amended safety assessment published in 2000, the Panel concluded that Glyoxal is safe for use in products intended to be applied to the nail at concentrations ≤1.25%; however, the available data were still insufficient to support the safety for other uses. According to the Dictionary, Glyoxal was reported to function as a fragrance ingredient and preservative in cosmetics. Anhydrous Glyoxal does not exist in a stable form at room temperature, and therefore it is commonly supplied in the form of an aqueous solution at 30%-50%. In a 5% solution, 39% of Glyoxal is present in the monomer form; in a 40% solution, the monomer content amounts to as little as 11% of Glyoxal, the dimer, and trimer forms being dominant. … [kırpıldı — bölüm toplam 18695 karakter]

In Vitro No published ocular irritation studies were discovered and no unpublished data were submitted. Animal A solution of 32.8% aqueous Glyoxal caused grade 5, out of 20, injury to the eyes of rabbits.2 Glyoxal (30%) caused moderate irritation in the rabbit eye that cleared within 48 h without permanent injury. When Glyoxal (40%) was instilled into one conjunctival sac of each of three rabbits, no changes in the iris or corneal opacity were noted. Well-defined redness and chemosis of the conjunctiva was noted in all three treated eyes at the 1-h observation. The reactions were scored as slight at the 72-h reading and as normal at the day 8 observation. Glyoxal powder was a severe ocular irritant when instilled into the conjunctival sac of rabbits. Reactions produced had an average 1-h maximum score of 65.6 out of a maximum possible 110. Glyoxal powder was classified as a slight ocular irritant with an average 1-h maximum score of 6.6. In an ocular irritation study performed in accordance with OECD GL 405 (Acute Eye Irritation/Corrosion) using rabbits, Glyoxal (40%) caused reversible reddening and chemosis of the conjunctiva within 8 days and thus showed an irritating effect.8 The instillation of Glyoxal (30% or 40% aqueous; 0.05 mL) into the conjunctival sac of rabbits caused a slight to strong reddening, mild edemas, and inflammation as well as a hazy clouding of the cornea depending on the concentration.8 These effects were resolved within 1 or 2 weeks. In a comparative study between “pure” Glyoxal (40% aqueous; 0.05 mL) and “raw” Glyoxal (40% aqueous; 0.05 mL; no data on the impurities) on the eyes of rabbits, the instillation into the conjunctival sac caused a clear reddening and very strong inflammation on the conjunctiva.8 After installation of pure Glyoxal, a temporary, hazy corneal clouding … [kırpıldı — bölüm toplam 2308 karakter]

Irritation In Vitro No published in vitro irritation studies were discovered and no unpublished data were submitted. Animal In dermal studies, Glyoxal powder was not an irritant whereas 40% Glyoxal solution produced negative to moderate irritation in rabbits. Two different grades of Glyoxal (“pure” 30% or 40% aqueous and “raw” at 40% aqueous; no further information/characterization was provided) were administered to the shaved back skin of white rabbits (n not specified) and covered with cotton patches (approximately 2.5 cm2) in a patch test.8 The patches were left in place for 1, 5, and 15 min and 20 h. After the three shorter exposure periods, the treated skin was washed with undiluted polyethylene glycol 400 and then with a 50% aqueous polyethylene glycol 400 solution. The test site was not washed after the 20-h treatment period. In addition, the ear of each rabbit was treated with the test substance for 20 h. For an application period of 1 and 5 min, no or slight erythema with a yellowing of the skin could be observed 24 h after exposure for all three test substances. For the treatment period of 15 minutes, a mild edema was also noted for all test substances at all concentrations. Eight days after treatment, a yellowing and scaling of the skin at the test site was observed noted for all test substances at all concentrations. The 20-h exposure caused a slight, in some cases also a strong, erythema and edema formation for all test substances at all concentrations. After 8 days, a scaling of the skin, scab formation and a superficial necrosis were observed noted at all test concentrations. The 20-h exposure of the rabbit ear caused erythema and inflammation as well as minor skin defects 24 h after the application (no further details were provided). After 8 days, scab formation and a slight necrosis were observed for all test substances at all concentrations. No significant differences could be found between the 30% and 40% aqueous … [kırpıldı — bölüm toplam 7128 karakter]

No new published dermal carcinogenicity studies were discovered and no new unpublished data were submitted. Dermal Groups of mice were treated three times weekly throughout their lifetime with one of two Commercial 40% Glyoxal solutions (1:8 dilution in water; effective concentration was 4.5%) to the clipped skin of the back.2 Treated mice had longer mean survival times than did the controls. Neither dermal nor subcutaneous neoplasms were found in mice treated with Aerotex Glyoxal 40. Dermal inflammation and necrosis were observed in 10 of the 40 mice. Epidermal hyperplasia was noted in two mice. Similarly, no skin neoplasms were found in mice treated with European Glyoxal 40. One mouse of this group had an infiltrative fibrosarcoma; this neoplasm type occasionally occurs in control mice. No neoplasms were observed in control mice. Mice were shaved and painted with 500 µmol 40% aqueous Glyoxal for 5 weeks. Half of these mice were painted with a known tumor promoter, 12-0-tetradeconaylphorbol-13-acetate (TPA). There was no induction of neoplasms in mice treated with Glyoxal and TPA when compared to mice treated with Glyoxal alone, DMSO and TPA, or TPA alone. Rats were dermally treated with 100 mg/L N -methyl-N' -nitro-N-nitrosoguanidine (MNNG) and 10% sodium chloride via drinking water for 8 weeks. Other rats were given drinking water for 8 weeks. After this, animals were dosed with 0.5% Glyoxal via the drinking water for 32 weeks, and then killed for necropsy. Animals dosed with Glyoxal after initiation had an increase in hyperplasia and carcinoma of the pyloric region and hyperplasia of the fundic region of the stomach. Neither hyperplasia nor carcinomas were seen in animals that were not treated with MNNG, suggesting Glyoxal may act as a promotor not as an initiator. Oral An 8-week liver bioassay was used to detect potential hepatocarcinogenic activity in the constituents of coffee.2 One … [kırpıldı — bölüm toplam 6129 karakter]

Cited by 77. Methylglyoxal, a known endogenous and environmental mutagen, is a reactive alpha-ketoaldehyde that can modify both DNA and proteins. To investigate the possibility that methylglyoxal induces a crosslink between DNA and DNA polymerase, we treated a 'primed template' DNA and the exonuclease-deficient Klenow fragment (KF(exo-)) of DNA polymerase I with methylglyoxal in vitro. When the reaction mixtur

EPA ToxValDB skin/eye data — endpoint: Skin Irritation, classification: Skin irritation - category 2. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Eye Irritation, classification: Eye irritation - category 2A. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Skin Sensitization, classification: Sh. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Skin Sensitization, classification: Skin Sens. 1. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Eye Irritation, classification: Category 6.4A (Category 2A). Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.