Silica gel causes cancer


24. TRK value for 4,4'-diaminodiphenylmethane: 0.1 mg / m3

(BArbBl. 10/89 p. 61)


In the list of carcinogenic hazardous substances, 4,4'-diaminodiphenylmethane is classified in group III (hazardous) with a mass content of 1%. Synonyms for 4,4'-diaminodiphenylmethane are: DDPM, phenyl base, 4,4'-methylenedianiline, MDA

Occupational medical experience

4,4'-Diaminodiphenylmethane is absorbed by inhalation, through the skin and from the gastrointestinal tract.

The need to comply with protective measures during the industrial processing of 4,4'-diaminodiphenylmethane was pointed out as early as 1966 [5].

Yellow discolouration of skin, hair and fingernails is an indication of inadequate occupational hygiene [3].

There have been observations of a sensitizing effect on the bronchial tree [2] and photosensitization of the skin in the sense of a contact allergen [8].

The main systemic effects after absorption are toxic effects on the liver. Kopelman et al. [6] reported in 1966 on 84 cases of febrile jaundice, which were caused in England, in the Epping area, by 4,4'-diaminodiphenyl-methane-contaminated flour. ("Epping Jaundice").

The level of uptake of 4,4'-diaminodiphenylmethane could no longer be determined, a bread analysis showed about 0.26% 4,4'-diaminodiphenylmethane.

In spite of marked increases in liver enzymes and bilirubin, and in some cases demonstrated histological changes in the liver, all symptoms regressed. Follow-up examinations after 2 years did not reveal any pathological findings.

McGill [9] reported in 1971 on 12 cases of "toxic hepatitis" in the production of synthetic resins based on 4,4'-diaminodiphenylmethane. The skin was seen as an essential organ of absorption. Follow-up examinations after 9 months to 5 years showed no permanent damage.

Comparable experiences with 4 out of 6 persons employed in the processing of 4,4'-diaminodiphenylmethane were published in 1984 [1].

For preventive medical examinations of employees in the manufacture and processing of

4,4'-Diaminodiphenylmethane, no usable product-related pathological findings were obtained [7].

Toxic kidney damage was only observed in one of the cases reported by Epping Jaundice [6]; they seem to be dependent on high exposure.

There is no reliable knowledge about a carcinogenic effect in humans.

In the EPA study [4] only a study by Scott-Siegel from 1984 is reported. When calculating the proportional mortality rate (PMR) and proportional cancer mortality rates (PCMR) on 179 workers who, among other things, had been handling 4,4'-diaminodiphenylmethane, increased PMR values ​​were calculated for cancer of the bladder, colon and lymphosarcoma.

Only the increase in bladder cancer was significant in the PCMR. The observation is attributed to the "structural similarity to benzidine". In the overall assessment, the informative value of the PMR and PCMR calculation for establishing a causal relationship in general and for the present study between increased bladder cancer rate and exposure to 4,4'-diaminodiphenylmethane is assessed as inadequate.

Further epidemiological studies on the question of the carcinogenicity of 4,4'-diaminodiphenylmethane in humans are not available.

Toxicological experience

4,4'-Diaminodiphenylmethane is toxic to the liver in humans and animals even at low doses. for longer oral administration to cats at 3 mg / kg daily and to rats at 8 mg / kg body weight. 4,4'-Diaminodiphenylmethane penetrates the intact skin.

A DNA-damaging effect was demonstrated in various in vitro test systems (Ames test, DNA strand breaks in mammalian cell cultures, mutations in yeast). After intraperitoneal injection into the mouse, sister chromatid exchanges were found in bone marrow cells. In the recessive lethal test on Drosophila and in cytogenetic studies on human lymphocytes in vitro (chromosome aberrations and sister chromatid exchange), however, no DNA damage could be found [10].

4,4'-Diaminodiphenylniethan showed a carcinogenic effect in several animal experiments. The concentrations of 150 and 300 ppm in drinking water led to increased thyroid tumors and neoplastic nodules in the liver in F344 rats. At the B6C3F1-Mouse, thyroid tumors as well as increased numbers of liver tumors were found under such conditions. Lymphoma. Phaeochromocytomas and lung adenomas, although both concentrations were clearly toxic. Oral administration of 30 mg / animal every 3rd day for 30 days with 9 months of follow-up led to increased mammary gland tumors in female Sprague-Dawley rats. After subcutaneous injection, 4,4'-diaminodiphenylmethane was slightly carcinogenic in the Wistar rat. while under similar conditions it did not show such an effect in the Sprague-Dawley rat, which is usually more sensitive to aromatic amines, despite twice the total dose. The administration of 70 mg 4,4'-diaminodiphenylmethane to 9 female beagle dogs three times a week for 4 - 7 years led to a deterioration of the general condition and to liver damage. but not to tumors [10].

The results of initiation / doctoral studies are inconsistent: After initiation with N-bis (2-hydroxypropyl) nitrosamine, 4,4'-diaminodiphenylmethane promoted the development of thyroid tumors, but not of liver and kidney tumors. After initiation with N-ethyl-N-hydroxyethylnitrosamine or N-butyl-N (4-hydroxybutyl) nitrosamine, 4,4'-diaminodiphenylmethane even led to a reduction in the number of liver, kidney and bladder tumors. After pretreatment with N-nitrosomorpholine, there was also no clear promotional effect on the liver [10].

Overall, the carcinogenic effect of 4,4'-diaminodiphenylmethane is relatively weak as far as we know.

Analytics

A recognized method according to ZH1 / 120 is available for measuring 4,4'-diaminodiphenylmethane in the air in work areas [11].

The determination limit of the method (sampling by adsorption on silica gel impregnated with sulfuric acid, Elutson, diazotization and coupling and subsequent photometric determination) is 0.1 mg / m3at 80l Sample air or 0.025 mg / m3320l Test air (8 hours).

Manufacture and use

4,4'-Diaminodiphenylmethane is produced by reacting aniline with formaldehyde in large-scale plants (amount: approx. 100,000 t / year) and is largely processed further by reacting with phosgene. Smaller quantities are used, among other things, for the production of dyes. Plastics and used as an epoxy hardener in wire enamels.

Results of the workplace measurements

Production of 4,4'-diaminodiphenylmethane

24 shift average values ​​(fixed and personal sampling) are available from the plants producing 4,4'-diaminodiphenylmethane. 19 values ​​are below the limit of quantification (0.025 mg / m3). In 5 cases values ​​from 0.1 to 1 mg / m3 determined.

Use of 4,4'-diaminodiphenylmethane

  • Implementation with phosgene
    With 14 shift mean values ​​(personal sampling) in two plants, no value above the limit of quantification was found.
  • Other processing
    In the area of ​​processing 4,4'-diaminodiphenylmethane in dye production and other processing, 12 shift average values ​​(personal sampling) were measured. The concentrations are below the limit of quantification. When a reaction vessel was filled in batches with powdered 4,4'-diaminodiphenylmethane, a concentration of 2.5 mg / m3established (duration of exposure 2 hours.
  • loading
    In connection with loading work, two short-term values ​​(less than 1 hour) of 0.05 mg / m3 measured.
literature

[1] Bastian, P. G. (1984) Occupational hepatitis caused by methylenedianiline.

Med. J. Aus. 8: 533-535

[2] Belin, L., Wass. U., Audunsson, G., Matthiasson, L. (1983) Amines: possible causative agents in the development of bronchial hyperreactivity; Brit. J. Ind. Med. 40: 251-257

[3] Deutsche Forschungsgemeinschaft (1987) Toxikolog.-Arbeitsmediz. Justification of MAK values

Edited by D. Henschler, VCH Verlagsgesellschaft mbH, D-6940 Weinheim

[4] Environmental Proteetion Agency (USA) (2.2.1985) Risk assessment for 4,4'-methylenedianiline. Office of Toxic Substances

[5] Hofmann, H. Th., Frohberg, H., Meinecke, K. H., Oettel, H., v. Schilling, B., Zeller, H. (1966) Potential health damage from 4,4'-diaminodiphenylmethane, its early detection and prevention.
15. Internat. Congress for occupational diseases. Proc-a III 194: 849 - 851 Vienna

[6] Kopelmann, H., Robertson, M.H., Sanders, P.G., Ash, J. (1966) The Epping-Jaundice. Brit. Med. J. I: 514-516

[7] Korallus, U. (1988) Unpublished observations

[8] Levine, M. J. (1983) Occupational photosensitivity to diaminodiphenylmethane.