Title: Benzotriazole and Tolyltriazole. Evaluation of health hazards and proposal of health based quality criteria for soil and drinking water Author
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TOXICOKINETICS 9 2.1 A BSORPTION , DISTRIBUTION 9 2.2 E LIM INATION 9 2.3 M ODE OF ACTION 9 3 HUMAN TOXICITY 10 3.1 S INGLE DOSE TOXICITY 10 3.2 I RRITATION 10 3.3 S ENSITISATION 10 3.4 R EPEATED DOSE TOXICITY 10 3.5 T OXICITY TO REPRODUCTION 10 3.6 M UTAGENIC AND GENOTOXIC EFFECTS 10 3.7 C ARCINOGENIC EFFECTS 10 4 ANIMAL TOXICITY 11 4.1 S INGLE DOSE TOXICITY 11 4.1.1 Inhalation 11 4.1.2 Oral intake 11 4.1.3 Dermal contact 12 4.2 I RRITATION 13 4.2.1 Skin irritation 13 4.2.2 Eye irritation 13 4.3 S ENSITISATION 14 4.4 R EPEATED DOSE TOXICITY 14 4.4.1 Inhalation 14 4.4.2 Oral intake 14 4.4.3 Dermal contact 16 4.5 T OXICITY TO REPRODUCTION 16 4.6 M UTAGENIC AND GENOTOXIC EFFECTS 16 4.7 C ARCINOGENIC EFFECTS 17 5 REGULATIONS 19 5.1 A M BIENT AIR 19 5.2 D RINKING WATER 19 5.3 S OIL 19 5.4 O CCUPATIONAL E XPOSURE L IM ITS 19 5.5 C LASSIFICATION 19 5.6 IARC 19 5.7 US-EPA 19 3 6 SUMMARY AND EVALUATION 20 6.1 D ESCRIPTION 20 6.2 E NVIRONM ENT 20 6.3 H UM AN EXPOSURE 20 6.4 T OXICOKINETICS 20 6.5 H UM AN TOXICITY 20 6.6 A NIM AL TOXICITY 20 6.6.1 Single dose toxicity 20 6.6.2 Irritation 21 6.6.3 Sensitisation 21 6.6.4 Repeated dose toxicity 21 6.6.5 Toxicity to reproduction 21 6.6.6 Mutagenic and genotoxic effects 21 6.6.7 Carcinogenic effects 22 6.7 E VALUATION 22 6.7.1 Critical effect and NOAEL 23 7 TDI AND QUALITY CRITERIA 24 7.1 TDI 24 7.2 A LLOCATION 24 7.3 Q UALITY CRITERION IN SOIL 24 7.3.1 Quality criteria in soil 24 7.4 Q UALITY CRITERION IN DRINKING WATER 25 7.4.1 Quality criterion in drinking water 25 8 REFERENCES 26 4 Preface The Danish Environmental Protection Agency has requested an evaluation of health hazards by exposure to Benzotriazole and Tolyltriazole and a proposal of health based quality criteria for soil and drinking water. This resulted in 2006 in the present report, which was prepared by Vibe Beltoft, Elsa Nielsen and Ole Ladefoged, Department of Toxicology and Risk Assessment, Danish Institute for Food and Veterinary Research, i.e. the present Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark. The report has been subjected to review and discussion and has been endorsed by a steering committee consisting of representatives from the following Danish authorities: The Danish Nature Agency, The Danish Ministry of Food, Agriculture and Fisheries (The Faculty of Agricultural Sciences), The Danish Veterinary and Food Administration, The National Board of Health, Denmark, Danish Regions (former Amternes Videncenter for Jordforurening) The Danish Environmental Protection Agency. The Danish Environmental Protection Agency Copenhagen, December 2013. 5 1 General description This document considers the toxicity of 1) benzotriazole and 2) tolyltriazole. The term tolyltriazole (CAS 29385-43-1) is generally used for the commercial mixture composed of approximately equal amounts of 4- and 5-methylbenzotriazole with small quantities of the 6- and 7- methyl isomers (TNO BIBRA 1998). 1.1 Identity Molecular formula: 1) C 6 H 5 N 3 2) C 7 H 7 N 3 Structural formula: 1) N N N H 2) N N N H CH 3 Molecular weight: 1) 119.13 2) 133.17 CAS-no.: 1) 95-14-7 2) 29385-43-1 Synonyms: 1) 1,2-Aminozophenylene Azimidobenzene Aziminobenzene Benzene azimide 1H-Benzotriazole 1,2,3-Benzotrazole Benztriazole Benzisotriazole 2) Methylbenzotriazole Methyl-1H-Benzotriazole Tolyltriazol 6 1.2 Physical / chemical properties Description: 1) Benzotriazole occurs as an odourless, white to light tan, crystalline powder. 2) Tolyltriazole occurs as tan to light brown granules with a characteristic odour. Purity: - Melting point: 1) 98.5 °C 2) 76-87 °C Boiling point: 1) 204 °C (at 15 mm Hg), 159°C (at 2 mm Hg) 2) 210-212 °C (at 12 mm Hg), 160°C (at 2 mm Hg) Density: 1) - 2) 1.24 g/ml Vapour pressure: 1) - 2) 0.03 mmHg ( Pa) (at 20 °C) Concentration of saturated vapours: 1) - 2) 39 ppm (220 mg/m 3 ) (calculated) (20 °C/760 mmHg) Vapour density: 1) 4.1 2) 4.6 (air = 1) Flash point: 1) - 2) 182.2 °C Flammable limits: - Autoignition temp.: - Solubility: 1) Water: 1-5 g/l (at 23.7 °C). Soluble in alcohol, benzene, toluene, chloroform, and dimethylformamide. 2) Water: <0.1 g/l (at 18 °C). Alcohol: >100 g/l (at 21 °C), acetone: >100 g/l (at 21°C). Soluble in methanol, isopropanol, ethylene glycol, toluene and methyl ethyl ketone. References: NTP (1991a), NTP (1991b), Merck Index (1996), HSDB (1998), TNO BIBRA (1998), Chemfinder (1999). 1.3 Production and use Benzotriazole is used as a component of aircraft de-icing fluid, pickling inhibitor in boiler scale removal, restrainer, developer and antifogging agent in photographic emulsions, corrosion inhibitor for copper, chemical intermediate for dyes, in pharmaceuticals, and as fungicide. (HSDB 1998). 7 Tolyltriazole is used as inhibitor of corrosion of copper and copper alloys, in antioxidants, and photographic developers (NTP 1991b). In Denmark, benzotriazole and tolyltriazole are reported to be used in small amounts (0.1-0.2 %) in de-icing fluids, e.g. propylene glycol (MST 1999). They are also used as a corrosion inhibitor in antifreeze chemicals containing glycol (MST 2000). 1.4 Environmental occurrence In Denmark, benzotriazole and tolyltriazole have been detected in drainage water from de-icing platforms in Kastrup Airport and in the ground water besides the platforms. Around 30 µg/l of benzotriazole and around 160 to 180 µg/l of tolyltriazole were measured in the ground water besides the platforms. (MST 1999). No further data considering environmental occurrence have been found. However, under laboratory conditions, neither barley nor tomatoes were effected by the exposure to benzotriazole (barley roots were dipped or the intact tomatoplants were sprayed). Also under laboratory conditions, different strains of fish were exposed for one day to 5000 or 10000 µg/l benzotriazole in an aquatic environment. Effects on behaviour were reported for fish exposed to 5000 µg/l, and mortality was observed among the fishes exposed to 10000 µg/l (no further data). (Ecotoxicology database as of September the 12 th 2000). 1.5 Environmental fate No data were found. 1.6 Human exposure No data were found. 8 2 Toxicokinetics 2.1 Absorption, distribution No data were found. 2.2 Elimination Benzotriazole was metabolised by rat liver microsomes in vitro to 4-hydroxy- benzotriazole and 5-hydroxy-benzotriazole (Hoffmann and Pooth 1982 - quoted from Patty 1994). 2.3 Mode of action No data were found. 9 3 Human toxicity 3.1 Single dose toxicity No data were found. 3.2 Irritation No data were found. 3.3 Sensitisation Four cases have been described, where patch tests revealed allergic type reaction to products containing benzotriazole (Ducombs et al. 1980). In one case, a male metal worker presented with contact dermatitis of the hands and forearms. Patch tests revealed allergic type reactions to lubricating oil used by the worker. Benzotriazole was isolated from this oil. Re-testing with benzotriazole gave a strong positive reaction and histology of the skin showed an eczematous reaction. In another case of a worker with eczema of the hands, face and neck patch tests were positive to benzotriazole as well as to other components of industrial greases to which the worker was in daily contact. Two other subjects with contact dermatitis had weakly positive tests with benzotriazole. Benzotriazole (1% in petrolatum) has been included in special patch test series for car mechanics and metal workers with contact dermatitis. None of the 145 patients reacted to benzotriazole in 48-hour covered patch tests. (De Boer et al. 1989, Meding et al. 1994). 3.4 Repeated dose toxicity No data were found. 3.5 Toxicity to reproduction No data were found. 3.6 Mutagenic and genotoxic effects No data were found. 3.7 Carcinogenic effects No data were found. 10 |