Life cycle assessment of creosote-treated wooden railroad crossties in the US with comparisons to concrete and plastic composite railroad crossties.

A comparison of cradle-to-grave environmental life cycle assessments of creosote-treated wooden railroad crossties with concrete and plastic composite ties is presented in the Bolin and Smith article published in Journal of Transportation Technology. The assessment found that the manufacture, use and disposition of creosote-treated wooden crossties offers lower fossil fuel and water use and lesser environmental impacts than competing products manufactured of concrete or plastic composite.

Read: Life Cycle Assessment of Creosote-Treated Wooden Railroad Crossties in the US with Comparisons to Concrete and Plastic Composite Railroad Crossties

Creosote-Treated Ties: An End-of-Life Tie Evaluation

This article by Steve Smith and Chris Bolin reports some of the energy and environmental consequences of end-of-life options for creosote-treated wooden railroad ties when  taken out of service.  End-of-life alternatives include recycling ties to produce energy, disposal in landfills, and legacy ties along the railroad right-of-way.

Read: Creosote-Treated Ties: An End-of-Life Tie Evaluation

Review of Draft Pollution Prevention Management Strategies for Polycyclic Aromatic Hydrocarbons in NY/NJ Harbor proposed by Valle et al.

This critique, prepared by Waterborne Environmental, Inc., for the Creosote Council, details the various shortcomings in a report purporting to identify the sources of PAHs entering the New York/ New Jersey Harbor.

Read: Review of Draft Pollution Prevention Management Strategies for Polycyclic Aromatic Hydrocarbons in NY/NJ Harbor 

Creosote Treated Piling –Perceptions versus Reality

This paper by Dr. Kenneth M. Brooks explores the misconceptions people have regarding Creosote Treated Wood and what is really occurring in an aquatic environment

Read: Creosote Treated Piling – Perceptions versus Reality 

Polycyclic Aromatic Hydrocarbon Migration From Creosote Treated Railroad Ties Into Ballast and Adjacent Wetlands

Dr. Kenneth Brooks explores the impact of Creosote Treated Railroad Ties in a Wetland Environment. This study was funded by the United State Department of Agriculture with cooperation with the United State Department of Transportation.

Read: Polycyclic Aromatic Hydrocarbon Migration From Creosote Treated Railroad Ties Into Ballast and Adjacent Wetlands

Wong and Harris Study (PDF)

Dr. Wong reports on the cancer and noncancer death rates of creosote wood treating workers and finds that there is no evidence for an increase in death rate or early death by any cause as a result of occupational exposure to creosote in wood treating plants. Read: Wong and Harris Study.

Creosote, the Nose and Human Health (PDF)

The odor of creosote is easy to detect but is not cause for alarm. The odor of creosote is easily identifiable, for good reason: creosote has a very distinct odor, and the human nose is able to detect it at extremely low concentrations. But just because it may smell bad doesn’t mean it is bad! Read: Creosote, the Nose and Human Health

Creosote Toxicology and Risk Assessment

The potential for creosote to produce adverse health effects has been well-studied in laboratory testing and in human populations with occupational exposure to creosote.

The weight of evidence suggests that aside from skin conditions likely associated with chronic irritation and phototoxicity creosote does not pose significant cancer or other health risk to workers.

Creosote is a term applied to various unrelated substances including resin from the leaves of certain bushes, residue from burned wood, and coal tar distillation products. It has been erroneously assumed in some reviews of “creosote” that each of these substances or mixtures is practically identical to, if not interchangeable with the other in chemistry and toxicity. Compositionally, there is a clear qualitative and quantitative difference in the make-up of materials casually called “creosote”.  (See SCIENCE section). These differences manifest as differences in physical and biological properties.

This website is dedicated exclusively to coal tar creosote used to preserve wood and in this site the term “creosote” means coal tar creosote and nothing else. In this sense, “creosote” refers  to  a pesticide used as a wood preservative. Unlike most pesticides creosote is applied in a controlled and limited setting under closed process conditions.  This is the only permissible way creosote can be used as a pesticide. Railroad ties, utility poles and pilings are the wood products treated with creosote.  Wood treating workers generally receive greater exposure to creosote than any other group.  But exposures in wood treating plants are controlled to a larger degree than that for typical pesticide applications.

Creosote is a highly complex mixture containing hundreds of individual compounds. The actual chemical composition of creosote may vary somewhat due to differences in the coal source material. When used as a pesticide to preserve wood, creosote (CAS# 8001-58-9) can only be manufactured by the distillation of tar obtained from coal and it must conform to standards established by the American Wood Protection Association (AWPA, 1995), P1/P13 or P2. These standards identify the source material for pesticide creosote as well as the physical-chemical characteristics of the pesticide product. AWPA defines the P1/P13 and P2 (creosote) fractions for use as heavy duty wood preservatives as “a pure coal tar product, derived entirely from tar produced by carbonization of bituminous coal.” Compositionally, there are clear qualitative and quantitative difference in the make-up of creosote and other coal tar products such as pitch or roofing tar.

It has been erroneously assumed in some reviews of creosote that coal tar and coal tar products are practically identical to, if not interchangeable with, creosote in terms of chemistry and toxicity. What follows below is a summary of studies completed on creosote as used in the wood preserving industry and assessments of the health status of those who work with creosote in the wood treating industry.

Exposure Analysis

A study was recently conducted by the Creosote Council to determine the dermal and inhalation exposure creosote workers receive when engaged in wood preservation with creosote.  Four facilities in North America were studied for 5 days each. Air samples were collected on PFTE filters and XAD-2 resin and analyzed by gas chromatograph equipped with a flame ionization detector (GC/FID) for individual PAH components of creosote and for coal tar pitch volatiles (CTPV). Dermal sampling was conducted with whole body dosimeters (WBD) which are cotton long underware worn under regular work clothing and glove liners worn under gloves.  Analysis of  WBD sample was performed by gas chromatograph with a mass spectrometer detector (GC/MS).

The results of the study indicated that benzene, xylene and toluene were not detectable in the air at any plant site.  Airborne naphthalene was measured at each site and average concentrations ranged from 0.08 to 1.29 mg/m3. CTPV were nondetected at each site. Benzo(a)pyrene was nondetected in the air at each site.  In this study a total of 108 measurements were made for daily dermal dose for a variety of job activities using passive, whole-body dosimeters.  Total dermal doses were reported to range from 0.0141 to 49.6 mg/kg and showed great variability with job activity.  The highest creosote inhalation exposures for any work activity ranged from 150-500 µg/kg/day.

Epidemiology

Just as toxicology studies are performed in laboratory animals at very high dose levels in order to be able to observe a response if one can occur, health status studies in occupationally exposed groups can not only assess the overall health of the members of the group but also provide an indication of the potential of adverse health effects to occur in all exposed people. If those, albeit healthy, workers who receive the greatest exposure are unaffected by their exposure, then other individuals with much lower exposures can also expect to be free of effects of exposure. This concept can be extended to apply to nonoccupationally exposed people in the extremes of life or in any life stage, i.e., the very young, the elderly, pregnant women and nursing infants.

A number of studies, published and unpublished, purport to describe epidemiological findings of wood treating workers and other populations exposed to creosote and have been cited as such in scientific reviews and regulatory position papers.  Careful review of these studies reveals that, for the most part, many of these studies do not examine creosote-exposed populations and thus are of questionable use in trying to understand and evaluate the effects of creosote in humans. Of the epidemiological studies of creosote workers or individuals assumed to be exposed to creosote, little data exists to establish it as a chronic health risk. The weight of evidence suggests that aside from skin problems likely associated with chronic irritation and phototoxicity, creosote does not pose significant cancer or other health risk to workers.

This must be balanced with the observation that many of these studies have significant weaknesses that limits their utility in totally assessing the risks of creosote to humans. The numbers are often small, exposure to multiple compounds occurs, and exposure measurements were often not done or were subject to classification error. However, with the limited exposure potential associated with pressurized wood treatment and improved personal protection protocols, worker risks from creosote appears to be low. Other studies of creosote-exposed populations involve a form of creosote different than that used in North America, which again limits their usefulness for understanding potential risks to workers using P1/P13 and P2 creosotes.

A cross-sectional occupational health study was developed for the workers of nine wood preservative plants. The study was designed to identify any health problems that might be related to occupational exposure to creosote or pentachlorophenol exposure.  257 of the 351 employees (73%) of the workers at four plants participated. Medical examination of the workers showed occasional borderline abnormalities in specific tests. With the exception of the skin examination, the prevalence of these abnormalities was not in excess of that in the general population. Examination of the skin revealed a greater than expected prevalence of pustular eruptions that may have been related to exposures at the plants. No other body system showed an excess prevalence of toxic effects. There was no evidence of skin cancer, bladder cancer or lung cancer. In summary, the general health of the plant population was good and, except for effects on the skin, did not reflect the presence of adverse health effects from creosote or pentachlorophenol.

A second cross-sectional clinical morbidity (health examination) study of 329 workers at five high pressure Creosote/Coal tar wood preservation plants was conducted by Tabershaw. One of the plants used pentachlorophenol as a wood preservative in addition to using creosote/coal tar preservative. The examination of the creosote workers was directed toward evidence of pathologic and toxicologic processes in the lungs, liver, kidneys, bladder, blood cells and skin. Carcinogenic concern was directed toward the lung, bladder and skin. The 329 examined creosote workers came from five plants in five states and accumulated about 3000 person-years of employment at these plants. Half of the examined workers had been employed in the plant for over five years, 30% over 10 years, and 10% over 20 years. Three-quarters of those eligible for the examination participated with participation rates similar in each age group. The examinations revealed little evidence of occupational disease. The only clinical finding thought to result from occupational exposure was the presence of a pustular folliculitis found in the interior thigh of three per cent of the workers.  Examination of the lungs, liver, kidneys, and blood cells were normal.  Inconsistent  findings, probably random events due to chance, were noted from plant-to-plant.  Such findings could not be correlated to levels of exposure. No evidence of an elevated incidence of cancer was observed among these workers. No skin cancer was observed. This study revealed a three percent prevalence of  pustular folliculitis as the only finding thought to be related to the occupational exposures to creosote.

The epidemiology studies described above provide evidence for the absence of a cancer effect in humans occupationally exposed to creosote. Each of these studies is limited by the relatively small number of subjects included in the study. This limitation is overcome in a 2005 study completed by Dr. Otto Wong and his associates and published in the Journal of Occupational and Environmental Medicine (July, 2005,  47:7, 683-397). Dr. Wong reports on the cancer and noncancer death rates of creosote wood treating workers and finds that there is no evidence for an increase in death rate or early death by any cause as a result of occupational exposure to creosote in wood treating plants. To read Dr. Wong’s report, read: Wong and Harris Study.

Risk Assessment

A probabilistic cancer risk assessment was conducted by The Sapphire Group, Inc., Bethesda, Md. for occupational exposure to coal tar creosote during pressure treatment of wood. The purpose of the risk assessment is to characterize the nature and magnitude of the cancer risk that may be associated with occupational exposure to coal tar creosote during the pressure treatment of wood. This risk assessment followed the basic USEPA methodology for conducting cancer risk assessments. The lifetime average daily dose (LADD) derived from an exposure assessment was multiplied by a cancer slope factor (SF) quantified as a part of the dose-response assessment to estimate added lifetime cancer risk.

This assessment differs from the USEPA OPPTS Preliminary Risk Assessment for Creosote in two important ways. First, the creosote mixture as a whole was assessed for its cancer potency as opposed to the estimated risks posed by individual components of the mixture. This approach was adopted because experimental data indicate that exposure to the creosote mixture results in a toxicological response that is qualitatively and quantitatively different than that from exposure to individual carcinogenic PAHs (e.g., benzo(a)pyrene) found in creosote. Further, sufficient data are available for creosote and related coal tar products to support use of a surrogate approach. Second, probabilistic (i.e., Monte Carlo) methods were used in this risk assessment to characterize the variability and uncertainty associated with many of the required parameters.

In this cancer risk assessment, the dose-response relationship for tumor development was characterized by grouping the tissue sites in two ways based on repeated differences in modes of action: (1) point-of-contact tumors, which consisted of those in the forestomach and small intestines; and (2) systemic tumors, which consisted of those at all other tissue sites. Dose-response relationships for point-of-contact tumors and systemic tumors were characterized using the default dose-response model for cancer risk assessment (multistage) from USEPA’s BMDS program. The results of the dose-response analysis are summarized in the following table.

A limitation of the surrogate approach is that it relies upon the test results obtained for a single “standard” mixture, whereas exposure in the workplace can vary with respect to the chemical content of the mixture. To address this limitation, an evaluation of the content variation of creosote mixtures was conducted. The benzo(a)pyrene and chrysene content for two creosote mixtures was fairly similar and the variation low, suggesting that this would not be a significant impediment to using the surrogate approach to assess cancer risk.

Recent worker exposure studies have indicated that dermal exposure to creosote used in wood treatment contributes more significantly to the total body burden than respiratory exposures. For instance, 15 times more pyrene was absorbed through dermal uptake than through respiratory uptake in workers at a creosote wood impregnation plant (Van Rooij et al., 1993). A recent exposure study (described above) which integrated both the inhalation and dermal pathway for wood treatment workers exposed to coal tar creosote was used as the primary source of exposure information and dose estimation for this risk assessment. That study showed that while several non-carcinogenic PAHs were detected in air (primarily naphthalene and methyl naphthalenes), the most volatile carcinogenic PAHs (i.e., benzo(a)pyrene and chyrsene) were never detected. Coal Tar Pitch Volatiles (CPTV) and naphthalene when detected were always present below U.S. occupational exposure standards.

When calculated on the basis of measured skin contact, total dermal doses were reported to range from 0.0141 to 49.6 mg/kg. The surface dermal dose was adjusted for transdermal absorption to estimate the systemic dose from dermal absorption. Using the in vivo data to estimate absorption in rats (8.86%) and the in vitro to estimate the relative absorption between human and rat skin data (4.24%/34.3% = relative absorption of 0.124) the dermal absorption of creosote in human in vivo was estimated to be 1.1%  (8.86%*0.124). Normal distributions based upon the means and standard deviations were used to estimate the distribution for human in vivo absorption. Because wood treatment workers may engage in many different activities over the course of their occupational tenure, the data from the creosote worker exposures study were combined to generate a single distribution for dermal dose with the potential variability in exposure to creosote in the workplace addressed using probabilistic methods. With all of the measurements (including potential outliers), the data were found to be best described as a log-normal distribution (p=0.444, Chi-square test) with a mean and standard deviation of 0.98 and 3.85 mg/kg, respectively.

Although inhalation exposure to some creosote components is also likely during wood treatment, the worker exposure study found only non-carcinogenic PAHs in workplace air. These findings are similar to the results of Borak et al. (2002) and other studies. In evaluating the inhalation exposure pathway for carcinogens, a source of the carcinogenic PAHs is certainly present in the overall creosote mixture used for wood-treating; however, release to the environment (air) is apparently lacking due primarily to the low volatility of the more hazardous PAHs like B(a)P and to the lower temperatures at which creosote is applied to wood (documented by analytical air samples). Therefore, no worker exposure to carcinogenic PAHs can occur through inhalation of workplace air. Since the inhalation pathway for the carcinogenic components of creosote is incomplete, this exposure pathway was excluded from further assessment of carcinogenic risk for creosote wood-treating workers. Furthermore, no ingestion exposure to the carcinogenic components of creosote is anticipated or evaluated for wood-treating worker populations.

The resulting cancer risk estimates for occupational dermal exposure to the coal tar creosote mixture including or excluding a probabilistic (Monte Carlo) analysis of cancer slope factors are summarized in the following table.

Cancer Risk Distribution for Workers Exposed to Creosote

These estimates of cancer risk generally fall within the range of acceptable risk levels (1×10^-6 to 1×10^-4) employed by the USEPA for evaluating cancer risks encountered in the environment. The proper interpretation of these values is that, over the course of a working lifetime, wood treatment workers exposed to coal tar creosote as a consequence of their employment will experience no more than one to three additional cancers per 10,000 workers exposed, probably less than 4 per 10,000, and maybe zero. Since the most recent estimates suggest that no more than 3,700 total individuals currently work in the creosote wood treatment industry and of those only 390 to 600 individuals are actually involved in pressure treating with creosote, the upper-bound estimate suggests no additional cancer cases would result beyond the normal background incidence of between 98 and 125 cases of cancer in a population of this size.

The best estimate would suggest that no additional cases of cancer would occur in this population given the exposure potential and carcinogenic potency of creosote. The estimated workplace risks for creosote workers also fall well below the OSHA level of acceptable cancer risk in the workplace of 1×10-3 (Rodricks et al., 1987). Accordingly, the added cancer risk posed by exposure to creosote during wood pressure treatment operations falls well within normally accepted regulatory risk and thus poses no elevated cancer risk.

Health Effects Testing

Toxicological testing of both P1/P13 and P2 creosotes has been completed by the Creosote Council on bona fide AWPA P1/P13 and P2 composite test materials.  The composite creosotes, known as North American P1/P13 Composite Test Material and North American P2 Composite Test Material were formed by the North American creosote producers and importers who sell into the U. S. pesticide market. The studies, described below, have been developed with globally-accepted regulatory protocols (U. S. Environmental Protection Agency Office of Pesticide Programs testing guidelines) and have been certified to have been conducted and reported in compliance with U. S. Environmental Protection Agency Good Laboratory Practices Regulations.

Tests for Effects of Short-Term Exposure

Ingestion – the acute oral LD50 value for P1/P13 and P2 creosotes, respectively, is 2,197 and 2,236mg of creosote/kg of animal body weight.  This is a high value meaning that creosote is not very toxic to test animals following a single ingestion and that large amounts are required to produce lethality, the endpoint of the study. When test results of this magnitude are extrapolated to humans, creosote would be considered no more than moderately toxic as a consumer product. As a pesticide the Environmental Protection Agency has classified creosote as Toxicity Category III for oral toxicity. Category III pesticides are required to have the least restrictive Signal Word (CAUTION) on the product label and the least onerous label precautionary statements when precautionary statements are required.  All pesticides are required to have a Signal Word on the product label. “CAUTION” is the least restrictive Signal Word permitted (40 CFR 156.10h).

In animals nonlethal signs of acute oral toxicity of creosote included, among other signs, both increased and decreased defecation, decreased activity, anogenital staining, decreased grooming activity. All nonlethal signs were completely reversible.

The lowest creosote dose producing any signs of toxicity in animals was 1,000 mg/kg (decreased activity, material around mouth, low carriage, decreased defecation, decreased limb tone). This dose, 1,000mg/kg, is a nonlethal dose which causes only reversible effects. This dose corresponds approximately to a single oral dose of 70 grams in an adult human, or about 2.5 fluid ounces consumed at one time.

Dermal exposure – the 24-hour acute dermal toxicity values for P1/P13 and P2 creosotes is >2,000mg/kg. This dose, 2,000mg/kg applied to the shaved back of rabbits for 24 continuous hours under a bandage, is the maximum dose used in dermal testing. Undiluted creosote on the skin of rabbits for 24 hours produced no pharmacotoxic signs, no changes in body weight for two weeks following dosing, and no deaths in the test animals. Under these test conditions, creosote is nontoxic dermally. EPA classifies creosote as Toxicity Category III and requires “CAUTION” as a label signal word.

Eye irritation – undiluted P1/P13 and P2 creosotes were tested in rabbit eyes for irritation. The results indicated that P1/P13 creosote is mildly irritating to the eyes and P2 creosote is moderately irritating to the eyes. Animal eyes were evaluated for damage to the cornea, the iris and the conjunctiva. Evaluations were made using an ascending scale of 0 to 110. No corneal or iris changes were reported for either creosote at any time point (all scores “0”). Only conjunctival irritation was produced by direct introduction of liquid creosote into rabbit eyes: the irritation was completely reversible in 100% of the cases. The maximum irritation score for P1/P13 creosote occurred at 24 hours post-dosing and was 7.0 out of a possible 110.0. Eyes of all P1/P13-treated animals cleared by day 14 post-dose. The maximum irritation score for P2 creosote occurred at 1 hour post-dosing and was also 7.0 out of a possible 110.0. Eyes of all P2-treated animals cleared by day 7 post-dose. EPA has classified P1/P13 and P2 creosotes as Category II and III, respectively, for eye irritation.

Skin irritation – undiluted P1/P13 and P2 creosotes were tested on shaved rabbit skin for signs of irritation following four hours of exposure under a bandage.   P1/P13 and P2 creosotes were mildly irritating. Evaluations were performed at 1, 24, 48 and 72 hours post-application and 7 and 14 days post-application. Skin evaluations included appraisal of redness (erythema) swelling (edema) and other signs of skin damage such as fissuring, blistering, bleeding and necrosis. Slight to well-defined erythema and very slight-to-slight edema was observed in the test animals. These signs cleared in 11 of 12 animals by day 7 post-application; one animal showed erythema at day 14 post-application. There were no effects other than erythema and edema on the skin of any animal. The Primary Skin Irritation Index calculated for P1/P13 creosote in this study was 1.8 out of a possible 8.0, and for P2 creosote the Index was 1.5 out of a possible 8.0. These results place both P1/P13 and P2 creosotes in EPA pesticide category III for skin irritation, the least severe category used by EPA.  No label precautionary statements are required for this category.

Dermal sensitization – P1/P13 and P2 creosotes were evaluated for the ability to produce allergic skin sensitization in Guinea pigs. Neither P1/P13 or P2 creosotes produced signs of dermal sensitization in these studies meaning that these creosotes did not produce skin allergies in this test.

Inhalation – rats were exposed in whole-boy inhalation chambers to P1/P13 or P2 creosote aerosol and vapor for four hours. The P1/P13 exposures were to 5.0mg/L or 0.6mg/l and the exposures to P2 were to 5.3mg/L or 0.6mg/L. The creosote particle (droplet) size of the higher exposure was 2.9-3.4 micrometers (Mass Median Aerodynamic Diameter, MMAD) and 1.3 micrometers MMAD at the lower exposure concentration. At these particle sizes, about 2.5-4% of the particles were of a size to reach the rat alveolar space (respirable) at the high exposure and about 30% of the particles were respirable to the rat at the lower concentration. All particles were of a size to be inhaled into the rat upper and mid-respiratory tract. All animals survived the exposures; the significant pharmacotoxic signs following exposure included increased salivation and lacrimation, decreased activity, and decreased weight gain in some animals. All signs returned to normal during the 14 day observation period following exposures. There were no signs of exposure on gross necropsy at the end of the observation period. The acute inhalation LC50 value for P1/P13 and P2 creosotes determined in these studies was LC50 = >5mg/L, placing these creosotes in EPA Acute Toxicity Category IV. In an occupational setting, this level of exposure to airborne creosote is 400-times or more above the American Conference of Governmental Industrial Hygienists (ACGIH) recommended Threshold Limit Value (TLV) for long-term exposure to oil mist. This experimental creosote atmosphere covered the animal fur with creosote and darkened the exposure chambers interior and diffused light.

Tests for Effects of Repeated Exposure

Subchronic inhalation studies – Rats were exposed in whole body inhalation chambers to P1/P13 or P2 creosote for 6 hours/day 5days/week for 13 weeks.  The concentrations were 106, 59 and 5.4 mg/m3 for P1/P13 and 102, 48 and 4.7 mg/m3, respectively, for P2 creosote. Exposure to these levels of creosote (vapor and particulate) produced body weight loss or weight gain suppression in the top two exposure groups and staining of the animals’ respiratory tract and lungs immediately after the 90-day exposure period. Creosote deposition in the nose and upper respiratory tract produced acute and chronic inflammation which decreased along the tract toward the lungs. The lung changes were limited to pigment deposition characterized as trace level in severity. There were no lung inflammatory changes or lesions of any type. Several hematologic and serum biochemistry parameter changes were observed in the top two P1/P13 exposure groups and all P2 exposure groups. The changes were considered small by the study pathologist and reversed completely during the post-study recovery phase.  One high-dose and one mid-dose animal exposed to P1/P13 showed signs of myocardial degeneration. Thyroid changes (follicular cell hypertrophy) were noted in creosote-exposed animals; this condition was reversible in the animals exposed to P1/P13 creosote. In P2 creosote exposures, only the female animals were judged to have a creosote-related thyroid effect (follicular cell hypertrophy). Thyroid changes disappeared in the P1/P13 animals but remained in P2 female animals six weeks after the creosote exposures were terminated. Trace levels of pigment remained in the lungs and nose along with cyst formation in the nose. No changes indicative of heart damage were observed in any animal following the recovery period. Liver weight changes seen in P2-exposed animals were unaccompanied by histopathologic changes. At the end of the exposure period and at the end of the recovery period animals were evaluated by a veterinary ophthalmologist for signs of eye damage due to airborne creosote. No test material related eye changes were recorded. The NOAEL level in these studies were 5.4 and 4.7 mg/m3, for P1/P13 and P2 creosotes, respectively.

Subchronic dermal toxicity studies – Rats received a daily application of P1/P13 or P2 creosote to their skin at doses of 400, 40 or 4 mg/kg/day for 90 days. The creosote was applied under a bandage for the 6-hour exposure period. This treatment of animals produced essentially no effect other than slight skin irritation. One animal died during the study and according to the study pathologists, a mechanism of death could not be identified. All parameters for toxicity including ophthalmoscopic examination appeared to be completely unaffected by dermal creosote exposure, with the exception of transient weight loss in the high-dose P2 group.

Tests for Toxicity to Reproduction and the Developing Fetus

Developmental toxicity – Groups of pregnant rats received P1/P13 or P2 creosote oral on days 6 through 15 of their pregnancy and their pups were delivered by Cesarean section. The mothers were evaluated throughout the study for signs of adverse health effects (maternal toxicity) and the pups were evaluated for signs of developmental toxicity and skeletal or organ malformation. In the creosote developmental toxicity studies, P1/P13 creosote was dosed at 175, 50 and 25 mg of creosote/kg of animal body weight (mg/kg) and P2 creosote was dosed at 225, 75 and 25 mg/kg per day. P1/P13 creosote produced frank signs of maternal toxicity during pregnancy at the top dose of 175mg/kg/day. Developmental toxicity was manifest at the maternally toxic dose (175mg/kg) as an increased incidence of litter resorptions and decreased body weight for male fetuses. There were no structural defects produced at any dose level as a result of creosote administration. Adverse effects were not seen in the mothers or developing fetuses at the mid- and low-dose levels. This means that the developing fetus is not a special target for creosote toxicity and that measures to protect the adult from creosote overexposure will also protect the developing fetus.  P1/P13 creosote, therefore, is not considered a developmental toxicant.

P2 creosote produced maternal toxicity at all dose levels. Developmental toxicity was observed in the high-dose and was manifest as an increased incidence of post-implantation loss and litter resorption, reduced fetal body weight and reduced number of viable fetuses. There were no structural defects produced at any dose level as a result of creosote administration. Adverse effects were not seen in the developing fetus in the absence of maternal systemic toxicity. P2 creosote is, therefore, not considered as a developmental toxicant.

P1/P13 creosote was also evaluated for developmental toxicity in rabbits. Pregnant rabbits received 75, 9 or 1mg/kg creosote per day orally on days 6-18 of pregnancy. The high dose produced maternal toxicity as well as signs of developmental toxicity; however, none of the signs of fetal or developmental toxicity were statistically significantly different from the untreated control group incidence. As with the rats, adverse effects in rabbits were not seen in the mothers or developing fetuses at the mid- and low-dose levels of P1/P13 creosote. There were no structural defects produced at any dose level as a result of creosote administration.

Since damage to the embryo or the fetus did not occur with either creosote at dose levels that did not harm the mother, the embryo and developing fetus is not considered a target for creosote toxicity.

Reproductive toxicity – P1/P13 creosote was dosed orally to male and female rats and their offspring through two generations. The offspring of the initial set of animals in the study were potentially exposed to creosote through the placenta as a result of  maternal dosing, through possible transfer of creosote in milk during nursing (mothers were dosed daily with creosote during nursing) and then directly with creosote after weaning until they produced the next generation of pups. It is important to note that male animals were dosed with creosote as well in this study so that any potential adverse effect on male reproductive performance could be detected. The dose levels were 150, 75 and 25 mg/kg/day.

The NOAEL for adult systemic toxicity, reproductive toxicity, and developmental toxicity following daily oral gavage dosing was

Adult systemic toxicity consisted of food consumption and body weight changes, staining; developmental toxicity occurred at all dose levels as an increase in stillborn pups and reduced pup growth weight and viability. Reproductive effects (reduced pregnancy and copulatory induces) were seen only in the mid-dose level and only in the first generation pups.

No adverse reproductive or developmental effects were seen in the absence of parental l systemic toxicity.

Tests for Genetic Toxicity

Creosote has been evaluated in a number of in vitro mutagenicity tests, often  bacterial mutation tests, and usually with results indicative of a potential for genetic toxicity. Early results were equivocal due to difficulties with solubility of creosote in cell culture media. Dominant lethal mutation genetic toxicity testing in whole animals was performed by the Creosote Council. This testing is described below.

Dominant lethal mutation studies – P1/P13 creosote and P2 creosote were tested by oral gavage in rats for a male dominant lethal mutation effect. The study involves dosing the adult male daily for 7 days and then allowing the animal to mate with untreated females each week for ten weeks.  Ten weeks is the length of the sperm production cycle in rats. Animals in all dose groups for both creosotes showed pharmacotoxic signs following dosing and lost weight during the dosing period which was not recovered during the 10 weeks of mating following dosing.

P1/P13 was dosed at 857, 362 and 181 mg/kg/day in a rat dominant lethal bioassay. Animals in all dose groups showed pharmacotoxic signs following dosing and lost weight during the dosing period which was not recovered during the 10 weeks of mating following dosing.  P1/P13 creosote did not exhibit a dominant lethal effect and is considered negative for the induction of a germ cell mutation effect.

P2 was dosed at 866, 432 and 199 mg/kg/day in a rat dominant lethal bioassay. Animals in all dose groups showed pharmacotoxic signs following dosing and lost weight during the dosing period which was not recovered during the 10 weeks of mating following dosing. P2 creosote produced evidence of gem cell mutation (increase in dead implantation sites) at the high dose, a systemically toxic dose. The number of live implants was not significantly reduced and no dominant lethal effects were seen at weeks 8 or 9. P2 creosote is considered by the study director as negative for the induction of germinal chromosomal mutations in epididymal sperm, spermatids, and spermatocytes but positive in chromosome mutations in spermatogonial stem cells. Any effect in sperm stem cells was not manifest in mature sperm. In reviewing this study the US EPA concluded that “the number of live implant/female was not significantly reduced. In addition, no dominant lethal effects were seen at weeks 8 or 9, which would have included spermatogonial stem cells. Therefore, creosote P2 is considered to be negative for dominant lethal effects in rats”.

Historically, at least seven independently conducted studies have been conducted to assess the potential for creosote to induce tumor formation in test animals. While most of the early studies would not meet current standards, they are relatively consistent in terms of the biological response. These animal studies provide some insight into creosote’s hazard potential, however, uncertainty remains in the applicability of this data to man due to differences in products tested. i.e., the creosote used in 1940 may not be the same as that tested in 1996. The most relevant of these studies from a test material perspective is a dermal oncogenicity study performed by Creosote Council. In that study P1/P13 creosote was evaluated in a six-month skin cancer initiation-promotion study in mice. Creosotes have been tested in a number of skin cancer studies in rodents and in all but one case found to induce tumors at the site of application.  Since skin carcinogenesis is considered to be the result of several discrete biological steps (tumor initiation and tumor promotion), the 6-month study is an attempt to evaluate these steps separately. The study has a complicated design but essentially tests the potential of creosote to act as a tumor “initiator” or as a “promotor”, and as both. Under the conditions of the study, which were undiluted creosote or a 1% or 50% creosote suspension applied daily for two weeks followed by six months of twice-weekly applications, undiluted creosote was a skin irritant and acted as an initiator, a promoter and a complete carcinogen. These properties reduced or disappeared with lower doses of creosote.

Tests for Carcinogenicity

Data from these animal studies suggest that creosote (and other coal tar products) may pose a potential cancer hazard if the exposure is sufficiently high and duration sufficiently prolonged. Results from rodent bioassays on creosote must be interpreted with caution because in addition to uncertainty about the nature of the test material there are concerns about animal-to-man and high-dose to low-dose extrapolation methods. For instance, laboratory animals often quickly develop multi-system tumors in response to dosing with creosote or related coal tar products, a situation not seen in human populations exposed to relatively high levels for long periods of time. Since both oral and inhalation cancer bioassays of creosote and coal tar products display a non-linear dose-response relationship, this suggests that low doses may not be associated with a carcinogenic response. Many of the tumor responses in animals appear to be associated with chronic irritation and thus may be better correlated with cytotoxicity and resultant hyperplasia as a high dose phenomenon with limited relevance to the lower exposures that occur in the workplace. In the absence of a more thorough investigation of the mechanistic toxicity of creosote, the overall weight of evidence suggest that sufficiently high and prolonged exposure to creosote (and related coal tar products) may pose a potential cancer risk based primarily on animal evidence that has uncertain relevance to human exposure.