Contribution of polycyclic aromatic hydrocarbons and polar polycyclic aromatic compounds to the carcinogenic impact of flue gas condensate from coal-fired residential furnaces evaluated by implantation into the rat lung.

For identification of the substances chiefly responsible for the carcinogenic action of the emission condensate from coal-fired residential furnaces, the implantation method was used as a carcinogen-specific bioassay for comparison of the carcinogenic effect of various fractions with that of a total sample of flue gas condensate tested in 2 or 3 different doses. After implantation into the lungs of Osborne-Mendel rats, the condensate from coal-fired residential furnaces, a fraction containing polycyclic aromatic hydrocarbons (PAHs) and thiaarenes [sulfur-containing polycyclic aromatic compounds (S-PACs)] with 4-7 rings, as well as fraction containing more polar polycyclic aromatic compounds (PACs) and PAHs with higher molecular weight, induced lung carcinomas and sarcomas. According to probit analysis, the fraction containing PAHs plus S-PACs with 4-7 rings accounted for about 68.2% of the total carcinogenicity of flue gas condensate, whereas the fraction containing more polar PACs and higher PAHs accounted for about 54.6%. All other fractions, such as nonaromatic compounds and PACs with 2 and 3 rings, constituting about 70% of the weight of the total condensate, seemed not to be carcinogenic. Only 1.4% of the total carcinogenicity of the flue gas condensate was found to be attributable to the amount of benzo[a]pyrene (CAS: 50-32-8) present in the condensate (1.14 mg/g condensate). The contribution of more than 100% of both active fractions to the total carcinogenicity (68.2 and 54.6%) may suggest an interrelation of the fractions.

Local application to mouse skin as a carcinogen specific test system for non-volatile nitroso compounds.

Using the epicutaneous test as an experimental model for detecting carcinogenicity, 3 doses each of nitrosomethylurea (NMU), nitrosonornicotine (NNN) and nitrosocarbaryl (NC) were administered to the skin of 65 female CFLP mice/group. To compare the carcinogenic potency of the nitroso compounds, benzo[a]pyrene (BaP) was taken as reference substance. Dose-response relationships were obtained for NMU and NC as well as for BaP. NNN exhibited only a weak carcinogenic effect in the dose range from 12.5 micrograms to 200 micrograms tested in the skin painting model. It showed, however, no dose dependent activity. After probit analysis of the results, the carcinogenic potencies of the nitroso compounds investigated in this system rank as follows: NC, 0.18; NMU, 0.04; NNN, 0.008 (BaP, 1.00).

The contribution of polycyclic aromatic hydrocarbon fractions with different boiling ranges to the carcinogenic impact of emission condensate from coal fired residential furnaces as evaluated by topical application to the skin of mice.

Flue gas condensate from briquet-fired residential furnaces was separated into a polycyclic aromatic compound (PAC)-free and a PAC-containing part, followed by a subfractionation of the PAC-containing fraction into 3 parts: PAC consisting predominantly of (a) 2 and 3 rings, (b) 4 and 5 rings and (c) 6 and more rings. To evaluate the carcinogenic potency of the condensate and its fractions, local application onto skin of mice in 2 or 3 doses was used. Since it was known from an earlier investigation that both the PAC-free fraction and the fraction containing PAC with 2 and 3 rings were almost ineffective, only PAC-fractions containing more than 3 rings were tested. The probit and Weibull analysis of the results showed that the condensate and the fractions containing PAC with 4 and 5 rings as well as 6 and more rings provoke local tumors after repeated application to the dorsal skin of mice. The tumor incidence exhibited a clear cut dose-response relationship. Fractions (b) and (c) were almost equally active, each contributing by about 50% to the total carcinogenicity. The content of benzo[a]pyrene (0.72 mg/g condensate) contributed by 10-11% to the total carcinogenicity of the emission.

Investigation on the carcinogenicity of emission condensate from brown coal-fired residential furnaces applied to mouse skin.

Flue gas condensate emitted from brown coal-fired stoves was tested in 3 dosages applied chronically to the skin of female CFLP mice twice a week over a period of 104 weeks. To answer the question which portion of the total carcinogenicity results from benzo[a]pyrene (BaP), this compound was taken as reference substance. The probit and Weibull analysis of the results showed a linear dose-response relationship for both tumor incidences and tumor induction times. The amount of BaP in the emission condensate (0.593 mg/g condensate) contributes about 15% to the total carcinogenic effect of the brown coal flue gas condensate.

The contribution of polycyclic aromatic hydrocarbons to the carcinogenic impact of emission condensate from coal-fired residential furnaces evaluated by topical application to the skin of mice.

The objective of this investigation was to identify the substances chiefly responsible for the carcinogenicity of the emission condensate from coal-fired residential furnaces. To realize this, the carcinogenic effect of various fractions was compared with that of an unseparated sample of emission condensate, tested in different doses. The probit and Weibull analysis of the results showed: (1) The condensate emitted from a coal fired residential furnace as well as the reconstituted condensate combining all fractions, provoked local tumors after repeated application to the dorsal skin of mice. The tumor incidence exhibited a clear cut dose-response relationship. (2) The fraction of polycyclic aromatic hydrocarbons (PAH) and thiaarenes with more than three rings accounted for almost the total carcinogenicity (109-118% compared with the total condensate) of the emission condensate from the coal-fired residential furnace. (3) The fraction containing azaarenes and nitroarenes (NO2-PAH) accounted only for 4-7% of the total carcinoma incidence of the emission condensate. (4) The content of benzo[a]pyrene (0.702 mg/g condensate) contributes 10-11% to the total carcinogenicity of the emission condensate. (5) The PAH-free fraction and the fraction containing PAH with 2 and 3 rings (together about 77% by wt) were almost ineffective. No cocarcinogenic activity of this fraction was obtained, since the total condensate, as well as the PAH-fraction consisting of more than three rings applied proportionally provoked about the same carcinoma incidence.

Contribution of polycyclic aromatic hydrocarbons to the carcinogenic impact of gasoline engine exhaust condensate evaluated by implantation into the lungs of rats.

An attempt was made to identify the substances chiefly responsible for the carcinogenicity of gasoline engine exhaust condensate. A carcinogen-specific bioassay was performed by a comparison of the carcinogenic effect of various fractions with that of a total sample of automobile exhaust condensate, tested in two or three different doses. The results were examined by Probit analysis. After implantation into the lungs of OM rats, the condensate emitted from a gasoline-driven automobile and the fraction of polycyclic aromatic compounds consisting of more than 3 rings induced lung carcinomas and sarcomas. The tumor incidence demonstrated a clear-cut dose-response relationship. The fraction of polycyclic aromatic hydrocarbons (PAH) consisting of more than 3 rings accounted for about 81% of the total carcinogenicity of automobile exhaust condensate. This fraction represented only 2.8% by weight of the condensate. The content of benzo[a]pyrene (CAS: 50-32-8; 0.483 mg/g condensate) accounted for 2.4% of the total carcinogenicity of automobile exhaust condensate. Regarding the minor effect of the PAH-free fraction (approximately equal to 87% by wt), no evidence of cocarcinogenic activity was observed, since the total condensate as well as the PAH fraction consisting of more than 3 rings applied proportionally caused about the same tumor incidence.

On the contribution of polycyclic aromatic hydrocarbons to the carcinogenic impact of automobile exhaust condensate evaluated by local application onto mouse skin.

The objective of this investigation was to identify the substances chiefly responsible for the carcinogenicity of automobile exhaust condensate using topical application onto the skin of mice. This was performed by comparing the carcinogenic effect of various fractions with that of an unseparated sample of automobile exhaust condensate, tested in 3 different doses. The probit and Weibull analysis of the result shows: (a) The condensate, emitted from a gasoline-driven automobile provokes local tumors after long-term application to the dorsal skin of mice. The tumor incidence demonstrates a clear cut dose-response relationship. (b) The fraction of polycyclic aromatic hydrocarbons (PAH) containing more than 3 rings accounts for about 84-91% of the total carcinogenicity of automobile exhaust condensate. This fraction represents only about 3.5% by wt of the condensate. (c) The content of benzo[a]pyrene (BaP) (0.414 mg/g) accounts for 6-7.6% of the total carcinogenicity of automobile exhaust condensate, 15 selected PAHs for about 41%. (d) Regarding the minor effect of the PAH-free fraction (about 83% by wt), no hints for a cocarcinogenic activity were observed.

Experimental studies in rat lungs on the carcinogenicity and dose-response relationships of eight frequently occurring environmental polycyclic aromatic hydrocarbons.

The biologic activity of eight highly purified polycyclic aromatic hydrocarbons (PAH) widely distributed in the human environment was tested in the respiratory tracts of rats. These studies were performed for the examination of carcinogenic activity of the compounds and determination of a dose-response relationship. The lung implantation method was used in 3-month-old female OM rats. A dose-response relationship was obtained for benzo[a]pyrene (BaP), anthanthrene (ANT), benzo[b]fluoranthene (BbF), indeno[1,2,3-cd]pyrene (IND), benzo[j]fluoranthene (BjF), and benzo[k]fluoranthene (BkF). Benzo[e]pyrene and benzo[ghi]perylene showed no tumor-producing effect in this system when given at doses of 5 mg. The histologic and mathematical evaluations indicated that the investigated compounds had distinct carcinogenic potencies. After probit analysis of the results, the carcinogenic potencies of PAH investigated in the lung implantation model rank as follows: BaP, 1.00; ANT, 0.19; BbF, 0.11; IND, 0.08; BkF, 0.03; and BjF, 0.03.

Inventory and biological impact of polycyclic carcinogens in the environment.

The rapid development of the natural sciences and the technical progress during the last century have significantly changed our society and environment. During this period the average life expectancy for people in industrialized countries has doubled. A prolongation of life expectancy to this extent, due to for example, understanding of the relationship between various diseases and their corresponding causative agents, had never before occurred in mankind's history. It resulted in specific hygiene precautions. The recognition of such causal relationship was facilitated by the fact that infection diseases generally become apparent after a short incubation time, i.e. that an environmental situation causes health damage. At present, we are searching for origins of diseases of which the causal correlations with environmental influences are far more difficult to recognize than those of infection diseases, since long-term effects have to be observed. Do we have a situation similar to that which we had for infections at the end of the last century ? For diseases such as lung and larynx cancer, there are significant indications of carcinogenic compounds in the environment. Since both types of cancer are about 10 times more common among cigarette smokers who inhale than among non-smokers, a correlation to the risk factor "smoking" is beyond doubt. Living and working in larger cities or highly populated areas are additional factors which many enhance the lung cancer incidence ("urbanisation factor"). The air quality of these areas is supposed to be the reason for this effect. However, the present "bad air quality" at most doubles the disease incidence. A large number of epidemiological studies report on local differences of the incidence rates as well as significant increases or decreases of the mortality rates for some cancer diseases during comparatively short periods. A summary recently has been published by Misfeld (1). As an example, the mortality rate due to lung cancer for males in the F.R.G. has almost doubled during 1955-1975 from 36.5 per 100,000 to 65.9 per 100,000. This holds true for cancer of the rectum which increased from 8.8 per 100,000 to 18.9 per 100,000 during the same period. In contrast, mortality due to stomach cancer decreased from 59.3 to 36.6 per 100,000 and uterine cancer in females decreased from 16.6. to 8.5 per 100,000 (2). The pronounced changes in mortality rates cannot be explained by alterations of the genetic disposition during such a short period. Improved diagnostic and therapeutic techniques might explain decreases but not increases of mortality rates.(ABSTRACT TRUNCATED AT 400 WORDS)

Quantification of the carcinogenic effect of polycyclic aromatic hydrocarbons in used engine oil by topical application onto the skin of mice.

The purpose of this investigation was to identify the substances mainly responsible for the carcinogenic effect of used engine oil from gasoline engines using topical application as a carcinogen-specific bioassay. This was performed by comparison of the tumorigenic effect of single fractions with that of an unseparated sample of the lubricating oil. The probit analysis of the results shows: 1) The used engine oil, from gasoline-driven automobiles, investigated provoked local tumors after long-term application to the dorsal skin of mice. The incidence of carcinoma depended on the dose of the oil. 2) The fraction of the polycyclic aromatic hydrocarbons (PAH) containing more than three rings accounts for about 70% of the total carcinogenicity in the case of crankcase oil. This fraction constitutes only up to 1.14% by weight of the total oil sample. 3) The content of benzo(a)pyrene (216.8 mg/kg) accounts for 18% of the total carcinogenicity of the used oil. 4) Regarding the reduced carcinogenicity of the oil sample, which was reconstituted from all fractions, it seems possible that some of the carcinogenic substances were lost due to volatility, with evaporation of the solvents from the oil-fractionation processes. 5) Regarding the small effect of the PAH-free fraction, as well as the equal carcinogenic effects of the PAH-fraction (containing more than three rings) and the reconstituted oil sample, no hints for a co-carcinogenic activity were obtained.

Local carcinogenicity os some environmentally relevant polycyclic aromatic hydrocarbons after lifelong topical application to mouse skin.

Six environmentally relevant polycyclic aromatic hydrocarbons were tested in dose-response experiments of topical application to mouse skin with regard to local carcinogenicity: benzo(a)pyrene (BaP), benzo(b)- (BbF), benzo(j)- (BjF), and benzo(k)-fluoranthene (BkF), indeno(1,2,3,-cd) pyrene (IP), cyclopentadieno(cd)pyrene (CP), and coronene (COR). Of these compounds, BaP and BbF proved to be carcinogenic, BjF and CP were weakly carcinogenic whereas BkF, IP and COR showed no cancer-inducing effects. In the dose range investigated BbF has about 1/3 and CP about 1/20 of the activity of BaP.

The tumor-producing effect of automobile exhaust condensate and fractions thereof. Part III: mathematical-statistical evaluation of the test results.

This paper deals with the mathematical-statistical evaluation of experiments devoted to the following problems: 1. To what extent is the carcinogenic potency of automobile exhaust gas condensate dependent on the dose? 2. What fractions (groups of substances) of the automobile exhaust gas condensate are mainly responsible for the carcinogenic potency? 3. To what extent can the potency be explained by fractions (or single substances)? In order to answer the above questions, the working group planned animal experiments (cf. Misfeld and Timm, 1973) and obtained, prepared, and fractionalized automobile exhaust gas condensate (Grimmer, 1978). The exhaust gas condensate and its fractions were dropped onto the skin of female CFLP mice (Brune et al., 1978). In view of the problems posed above, the aim of the mathematical-statistical evaluation was to establish the dose-response relations, to assess the combined effect, and to estimate the relative potency and the assumed potency. In particular, the hypothesis (basis for the separation process) that the potency of the entire exhaust gas condensate is mainly attributable to the fraction which contains the polycyclic aromatic hydrocarbons (nitromethane phase) was examined.

Tumours in mice after subcutaneous injection of automobile exhaust condensates.

Automobile exhaust condensate (AEC), either mixed with benzo[a]pyrene (BaP) or suspended or dissolved in tricaprylin, was injected subcutaneously into NMRI mice in a series of experiments. The addition of AEC decreased the incidence of tumours which developed with 30, 90 and 270 microgram BaP. Reduction of tumour incidence was proportional to the amount of AEC added. With an injection of 10 microgram BaP, the latent period was greatly increased when AEC was added, but the occurrence of tumours was the same. Components of AEC appear to inactivate BaP, at least temporarily. In further experiments AEC and nine fractions thereof were injected subcutaneously into mice. The fraction comprising only polycyclic aromatic hydrocarbons (PAH) induced the highest incidence of tumours. In contrast, when it was administered in combination with other fractions the PAH fraction was less active. Application of the products of further fractionation of PAH showed that polycyclic compounds with seven or more rings can also induce tumours in this model.

Investigations on the carcinogenic burden by air pollution in man. XIV. Effects of automobile exhaust condensate on the Syrian golden hamster lung.

Syrian golden hamsters were intratracheally instilled with 5 or 2.5 mg/animal of automobile exhaust condensate at two weekly intervals. Moribund animals were fixed by intravascular perfusion. Samples of lobar and segmental bronchi, as well as of peripheral lung tissue, were taken for electron microscopical examination. In addition, all organs were examined histologically. After a survival time of 30 to 60 weeks all animals developed multiple pulmonary adenomas, thus indicating a marked carcinogenic effect of automobile exhaust condensate.

[Experimental studies into syncarcinogenesis. 7th communication: Syncarcinogenic effects of polycylic aromatic hydrocarbons (PAH) in epicutaneous tests in mice]. / Experimentelle Untersuchungen zur Syncarcinogenese. 7. Mitteilung: Syncarcinogene Wirkung von polycyclischen aromatischen Kohlenwasserstoffen (PAH) im Epicutantest an der Mäusehaut

A mixture of 11 carcinogenic and noncarcinogenic hydrocarbons was applied to the shorn skin of the back of 3400 female NMRI-mice. The proportion of the hydrocarbons in the mixture corresponded to the analytical findings in condensates of cigarette smoke, automobil exhaust gas, and preservation curing smoke and tar. Antagonistic effects by the individual hydrocarbons in the mixture were not observed, on the contrary the substances in the mixture showed additive effects. There were no differences in the mode of action of the different mixtures.