4-Methylimidazole

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4-Methylimidazole
4-Methylimidazole.svg
Identifiers
CAS number 822-36-6 YesY
PubChem 13195
ChemSpider 12640 YesY
ChEBI CHEBI:40035 N
Jmol-3D images Image 1
Properties
Molecular formula C4H6N2
Molar mass 82.10 g mol−1
Appearance Slightly yellowish solid
Density 1.02 g/cm3
Melting point 46 to 48 °C (115 to 118 °F; 319 to 321 K)
Boiling point 263 °C (505 °F; 536 K)
Hazards
Flash point 157 °C (315 °F; 430 K)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

4-Methylimidazole, often abbreviated 4-MEI or 4-MeI, is a heterocyclic organic chemical compound with molecular formula H
3
C
C
3
H
3
N
2
or C
4
H
6
N
2
. It is formally derived from imidazole through replacement of the hydrogen in position 4 by a methyl group. It is a slightly yellowish solid.

4-Methylimidazole may be formed in the browning of certain foods through the Maillard reaction between carbohydrates and amino-containing compounds. In particular, it is found in roasted foods, grilled meats, coffee and in types of caramel coloring produced with ammonia-based processes.[1][2] It may arise also by fermentation.

Preparation and structure[edit]

4-Methylimidazole may be prepared using the Debus-Radziszewski imidazole synthesis, by reacting methylglyoxal with ammonia and formaldehyde.[3] It may also be prepared by the reaction of hydroxyacetone and formamide in ammonia.[4]

Small energy difference separates 4-methylimidazole from its tautomer 5-methylimidazole.[5]

Health concerns[edit]

Concern has arisen about the presence of 4-MEI in caramel color (which is the most-used food and beverage coloring), typically at a concentration between 50 and 700 ppm.[6] Dark beers and common brands of cola drinks may contain more than 100 μg of this compound per 12-ounce serving.[1]

At very high doses (360 mg/kg of body weight), 4-methylimidazole is a convulsant for rabbits, mice and chicks, and was the likely cause of acute intoxication observed in cattle fed with ammoniated, sugar-containing cattle feed supplements in the 1960s.[6] However, several studies found no ill effect in rats and dogs for the concentrations found in caramel coloring.[6] A study even found 4-MEI had an anticarcinogenic effect on rats.[1][7] It has been claimed, however, that the reduction in tumor rates seen by Chan and others were due to lower body weight rather than a true anticarcinogenic effect.[1]

A 2007 study by the National Toxicology Program (NTP) found that high doses of 4-MEI were carcinogenic in mice and in female rats.[8] The same study found no unusual lung tumors in mice and reduced tumors in rats.[9] Similar effects were observed for the isomer 2-methylimidazole, which is not found in caramel coloring.[10] Dose-related, statistically significant decreases in multiple tumors were observed in both male and female rats exposed to 4-MEI in the NTP bioassay. 4-MEI was associated with a 25-fold decrease in the incidence of mammary tumors among high-dose females.[9] NTP noted briefly that the decreases in certain tumors, including mammary tumors, were greater than could be attributed to body weight alone.[8] Reduced body weight offers a partial explanation for the reduction in tumors, but does not appear to be the primary cause of the decreased tumor incidences, indicating 4-MEI itself may possess an ability to prevent tumor formation.[9] In response to high 4-MEI levels used in studies, US FDA spokesperson Doug Karas stated, "[a] person would have to drink more than a thousand cans of soda in a day to match the doses administered in studies that showed links to cancer in rodents.” [11]

Based on these studies, caramel coloring of all types are considered safe and are approved by many leading regulatory agencies around the world, such as the European Food Safety Authority (EFSA), the US Food and Drug Administration (FDA) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and, most recently, the Brazilian Health Surveillance Agency (ANVISA). The European Union requires class III caramels to contain <200 mg/kg 4-MeI and class IV caramels to contain <250 mg/kg 4-MEI (color adjusted).[12][13]

In January 2011, California added 4-MEI to its list of probable carcinogens and stipulated 29 μg per day as the "No Significant Risk Level" intake.[14] This is considerably less than the mean intake of 4-MEI by regular cola drinkers.[1] The food industry has strongly opposed that decision, as it implies the need for additional warning labels on many products, and it disputes the validity of the NTP study.[1] According to Dr James Coughlin, a toxicologist who studies animal carcinogens, the risk posed by 4-MEI is even smaller than this government estimate suggests. In order for humans to reach the equivalent of even the lowest cancer-causing dose in mice, a woman would have to drink 37,000 cans (12 oz) a day for the rest of her life, and a man would have to drink 95,000 cans a day. These figures come from a slightly more conservative study of colas done last year that found an average of 130 μg of 4-MEI per can as opposed to the 138 μg found by CSPI.[15]

In March 2012, both Coca-Cola and Pepsi announced they had their caramel color suppliers modify their manufacturing processes to meet the new California standard; as of the announcement, the changes had already been made for beverages sold in California.[16] The recipe is not changing in Europe, so the 4-MEI level will remain the same.[17][18]

In July 2013, the Center for Environmental Health issued a press release claiming that an independent study found little or no 4-MeI in nine out of ten Coke products, but showed high levels of 4-MeI in all ten Pepsi products.[19] Soon after the report was made public, PepsiCo stated that their soft drinks will have reduced amounts of 4-MeI "by February 2014."[20]

Review in United States[edit]

In January 2014, a consumer review of various beverages in the United States reported measurements of the amounts of 4-MEI found in them.[21] The study found that Pepsi ONE and Malta Goya contain the chemical in excess of 29 micrograms per can or bottle, with that being California Proposition 65's daily allowed amount for foods without a warning label.[21] Various other media sources reported the story, noting that the FDA says that there is no reason to believe that the products tested are unsafe but that they are conducting additional safety studies on 4-MEI found in foods and beverages.[22][23][24]

Pepsi challenged the conclusions of this study because "the average amount of diet soda consumed by those who drink it is approximately 100 [milliliters] per day, or less than a third of a 12 [ounce] can".[21] Because of this, Pepsi argues, consumers of its beverage would not get 29 micrograms of 4-MEI when drinking them.

See also[edit]

References[edit]

  1. ^ a b c d e f Jacobson, Michael F. (2011). "Petition to Bar the Use of Caramel Colorings Produced With Ammonia and Containing the Carcinogens 2-Methylimidazole and 4-Methylimidazole". Center for Science in the Public Interest. Retrieved 2011-01-11. 
  2. ^ http://oehha.ca.gov/public_info/facts/pdf/4MEIfacts_021012.pdf
  3. ^ US 4377696, Fritz Graf, "Preparation of 4-methylimidazoles", issued 1983-03-22, assigned to BASF Aktiengesellschaft 
  4. ^ US 4803281, Walter Mesch, "Preparation of 4-methylimidazole", issued 1989-02-07, assigned to BASF Aktiengesellschaft 
  5. ^ G.-S. Li, M. F. Ruiz-López, B. Maigret "Ab Initio Study of 4(5)-Methylimidazole in Aqueous Solution" J. Phys. Chem. A, 1997, vol. 101, pp 7885–7892. doi:10.1021/jp971390n
  6. ^ a b c World Health Organization (1975) Toxicological evaluation of some food colours, enzymes, flavour enhancers, thickening agents, and certain food additives. Accessed on 2011-01-11.
  7. ^ P. C. Chan; G. D. Hills; G. E. Kissling; Nyska, A. (2008). "Toxicity and carcinogenicity studies of 4-methylimidazole in F344/N rats and B6C3F1 mice". Arch Toxicol. 82 (1): 45–53. doi:10.1007/s00204-007-0222-5. PMC 2366200. PMID 17619857. 
  8. ^ a b National Toxicology Program (2007) Toxicology and Carcinogenesis Studies of 4-Methylimidazole (CAS No. 822-36-6) in F344/N Rats and B6C3F1 Mice (Feed Studies). NTP report TR-535. Accessed on 2011-01-11.
  9. ^ a b c Murray, F.J. (January 2011). "Does 4-methylimidazole have tumor preventive activity in the rat?". Food Chem Toxicol. 49 (1): 320–2. doi:10.1016/j.fct.2010.11.010. PMID 21075160. Retrieved 15 Aug 2012. 
  10. ^ "2-Methylimidazole (2-MeI) is Not Present in Caramel Colors". Color Info. International Association of Color Manufacturers. 27 June 2012. Retrieved 15 Aug 2012. 
  11. ^ Armour, Stephanie (5 Mar 2012). "FDA Skeptical Chemical In Sodas Harm Consumers". Bloomberg.com. Retrieved 15 Aug 2012. 
  12. ^ "Commission Regulation (EU) No 231/2012 of 9 March 2012 laying down specifications for food additives listed in Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament and of the Council Text with EEA relevance". Official Journal L 083 , 22/03/2012 P. 0001 - 0295. European Parliament. 9 Mar 2012. Retrieved 15 Aug 2012. 
  13. ^ European Food Safety Authority (2004) Scientific opinion on the re-evaluation of caramel colours (E 150 a,b,c,d) as food additives. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Accessed on 2011-01-11.
  14. ^ "Specific Regulatory Levels Posing No Significant Risk: 4-Methylimidazole (4-MEI)". Proposition 65. OEHHA. 7 Oct 2011. Retrieved 15 Aug 2012. 
  15. ^ Goetz, Gretchen (12 Mar 2012). "Cola Carcinogen Debate Bubbles Over". Food Safety News. Retrieved 15 Aug 2012. 
  16. ^ "Coke and Pepsi change recipe to avoid cancer warning". Associated Press (London: The Guardian). 9 March 2012. Retrieved 2012-03-09. 
  17. ^ Associated Press in New York (9 March 2012). "Coke and Pepsi change recipe to avoid cancer warning". London: Guardian. Retrieved 9 March 2012. 
  18. ^ "Coke and Pepsi alter recipe to avoid cancer warning". BBC News. 10 March 2012. Retrieved 10 March 2012. 
  19. ^ "One Year Later, Pepsi Still Contains Cancer-Causing Food Coloring". Center for Environmental Health. July 2, 2013. 
  20. ^ Wong, Venessa (5 July 2013). "Pepsi Plans to Drop Disputed Cancer Chemical". Bloomberg Businessweek. Bloomberg L.P. Retrieved 13 July 2013. 
  21. ^ a b c "Caramel Coloring in Soda - Artificial Food Coloring". consumerreports.org. Consumer Reports. 23 January 2014. Retrieved 24 January 2014. 
  22. ^ Hudson, William, (video presented by Elizabeth Cohen) (23 January 2014). "Consumer Reports: Too many sodas contain potential carcinogen". cnn.com. Retrieved 24 January 2014. 
  23. ^ (video) James, Susan Donaldson (24 January 2014). "Consumer Reports Food Coloring Scare: No Need to Give Up Soda Just Yet". abcnews.go.com. Retrieved 27 January 2014. 
  24. ^ Pierson, David (23 January 2014). "Pepsi One contains higher levels of potential carcinogen, report says". Los Angeles Times (Los Angeles: Tribune Co). ISSN 0458-3035. Retrieved 24 January 2014. 

External links[edit]