2-naphthylamine

Structural formula
General
Surname	2-naphthylamine
other names	2-aminonaphthalene; β-naphthylamine;
Molecular formula	C 10 H 9 N
Brief description	colorless to reddish odorless crystals
External identifiers / databases
EC number	202-080-4
ECHA InfoCard	100,001,892
PubChem	7057
Wikidata	Q209450
properties
Molar mass	143.19 g mol −1
Physical state	firmly
density	1.049 g cm −3 (at 115.8 ° C)
Melting point	113 ° C
boiling point	306 ° C
solubility	poorly soluble in water
safety instructions
H and P phrases	H: 302-350-411
	P: 201-273-308 + 313
Toxicological data	727 mg kg −1 ( LD 50 , rat , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

2-Naphthylamine is a derivative of naphthalene . It belongs to the group of aromatic amino compounds . In addition to 2-naphthylamine, there is also the isomeric 1-naphthylamine .

history

As early as 1895, the surgeon Ludwig Rehn reported an increased incidence of "bladder tumors in fuchsin workers". Rehn suspected that the cancers were caused by aniline . However, it is now accepted that aniline has only a very low potential for the formation of bladder carcinomas . From 1925 in Germany, “diseases caused by nitro and amino compounds of the aromatic range” were recognized as an occupational disease in the First Occupational Disease Ordinance. In 1936 the title of the Ordinance on Occupational Diseases was changed to "Diseases caused by cancer or other neoplasms as well as changes in the mucous membrane of the urinary bladder caused by aromatic amines", which still exists in this form to this day.

Interestingly enough, no urinary bladder tumors have been caused by aromatic amines in the usual experimental animals, mice and rats . In 1938, WC Hueper and colleagues were able to trigger bladder cancer for the first time in animal models with 2-naphthylamine in experiments with dogs . To date, dogs and humans are the only known species that can develop bladder cancer induced by aromatic amines. The reason for this is that dogs have no activity on the enzyme N -acetyltransferase , which means that a safe detoxification of the aromatic amines via N -acetylation would be possible. In 1943 the production of 2-naphthylamine was stopped in Germany. Japan followed in 1972 as the last industrial nation.

Extraction and presentation

2-Naphthylamine can be produced by reacting 2-naphthol with ammonium zinc chloride at 200 to 210 ° C. If 2-naphthol is heated with ammonium acetate to 270 to 280 ° C, the acetyl derivative of 2-naphthylamine is formed.

toxicity

The tumors caused by 2-naphthylamine mainly develop on the urinary tract and there mainly on the urinary bladder . The malignant neoplasms sometimes develop only decades after contact with 2-naphthylamine. Broad-based, seated or pedicled papillomas are typical . There is also evidence that other tumors can also be caused by 2-naphthylamine. According to some studies, the individual metabolism plays a decisive role in the risk of disease .

2-Naphthylamine can evidently result from de-phenylation during the metabolism of N- phenyl-2-naphthylamine (PBNA), a rubber additive.

2-naphthylamine could be detected in tobacco smoke.

metabolism

2-Naphthylamine is excreted renally with a half-life of about seven hours . Two different metabolism steps are possible: N - acetylation or N - hydroxylation . The N -acetylation leads to an extensive detoxification of the substance, while the N -hydroxylation in the erythrocytes leads to N -nitroso-2-naphthylamine. The nitroso compound can bind to thiol groups of glutathione or also of hemoglobin . However, some of it is diverted to the kidneys as a conjugate with the glucuronic acid and released there again in the urine. This creates arylnitrenium ions that can react with the mucous membranes of the urinary bladder, for example , and can bind to proteins , but also DNA and RNA , which ultimately means a carcinogenic effect.

Individuals in whom the metabolism of 2-naphthylamine takes place preferentially via N -acetylation have a lower risk of 2-naphthylamine-induced cancer as a result.

use

2-Naphthylamine was previously used in the manufacture of azo dyes and as an anti- aging agent ( antioxidant ) in rubber . After reductive cleavage of azo groups, the substance must not be released from textiles or leather products that come into direct contact with human skin for a longer period of time (Appendix 1 of the Consumer Goods Ordinance ). Due to its carcinogenic effect, which has been proven in humans , it is hardly ever used industrially. It has largely been replaced by less dangerous substances.

Individual evidence

↑ ^a ^b ^c ^d ^e ^f ^g ^h Entry on 2-naphthylamine in the GESTIS substance database of the IFA , accessed on February 1, 2016(JavaScript required) .
↑ Entry on 2-naphthylamine in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
↑ Entry on 2-naphthylamine in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on July 31, 2018 or earlier.
^ ^A ^b T. Seidel: Risk factors of bladder carcinoma patients from an industrial region in Saxony-Anhalt. Dissertation, Martin Luther University Halle-Wittenberg, 2003.
↑ toilet Hueper include: Experimental production of bladder tumors in dogs by administration of beta-naphthylamine. In: J Ind Hygiene Toxicol 20, 1938, pp. 46-84.
↑ JE Sharer et al: Comparisons of phase I and phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey. In: Drug Metabolism and Disposition 23, 1995, pp. 1231-1241. PMID 8591724 .
↑ T. Weiss et al .: Dephenylation of the rubber chemical N-phenyl-2-naphthylamine to carcinogenic 2-naphthylamine: a classical problem revisited. In: Critical Reviews in Toxicology 37, 2007, pp. 553-566, PMID 17674211 .
↑ S. Ohnishi et al: Oxidative DNA damage induced by a metabolite of 2-naphthylamine, a smoking-related bladder carcinogen. In: Japanese Journal of Cancer Research 93, 2002, pp. 736-743, PMID 12149138 .
↑ N. Hauptmann and JC Shih: 2-Naphthylamine, a compound found in cigarette smoke, decreases both monoamine oxidase A and B catalytic activity. In: Life Sciences 68, 2001, pp. 1231-1241. PMID 11233991 .

literature

2-naphthylamines. In: Rep Carcinog. 10, 2002, pp. 161-162. PMID 15326682
JF Curtis et al: Prostaglandin H synthase-catalyzed ring oxygenation of 2-naphthylamine: evidence for two distinct oxidation pathways. In: Chemical Research in Toxicology 8, 1995, pp. 875-883. PMID 7492737
SP Adams et al .: Phosphatase activity in commercial spleen exonuclease decreases the recovery of benzo [a] pyrene and N-hydroxy-2-naphthylamine DNA adducts by 32P postlabeling. In: Analytical Biochemistry 219, 1994, pp. 121-130. PMID 8059938

[GESTIS-1] ↑ ^a ^b ^c ^d ^e ^f ^g ^h Entry on 2-naphthylamine in the GESTIS substance database of the IFA , accessed on February 1, 2016(JavaScript required) .

[CLP_100.001.892-2] Entry on 2-naphthylamine in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .

[3] Entry on 2-naphthylamine in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on July 31, 2018 or earlier.

[seidel-4] A ^b T. Seidel: Risk factors of bladder carcinoma patients from an industrial region in Saxony-Anhalt. Dissertation, Martin Luther University Halle-Wittenberg, 2003.

[5] toilet Hueper include: Experimental production of bladder tumors in dogs by administration of beta-naphthylamine. In: J Ind Hygiene Toxicol 20, 1938, pp. 46-84.

[6] JE Sharer et al: Comparisons of phase I and phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey. In: Drug Metabolism and Disposition 23, 1995, pp. 1231-1241. PMID 8591724 .

[7] T. Weiss et al .: Dephenylation of the rubber chemical N-phenyl-2-naphthylamine to carcinogenic 2-naphthylamine: a classical problem revisited. In: Critical Reviews in Toxicology 37, 2007, pp. 553-566, PMID 17674211 .

[8] S. Ohnishi et al: Oxidative DNA damage induced by a metabolite of 2-naphthylamine, a smoking-related bladder carcinogen. In: Japanese Journal of Cancer Research 93, 2002, pp. 736-743, PMID 12149138 .

[9] N. Hauptmann and JC Shih: 2-Naphthylamine, a compound found in cigarette smoke, decreases both monoamine oxidase A and B catalytic activity. In: Life Sciences 68, 2001, pp. 1231-1241. PMID 11233991 .