Softwood shavings (pine and cedar) have been used as bedding for animals because they are inexpensive, have natural insecticidal and barteriocidal properties, and often effectively control odor. The fact that these beddings contain chemicals capable of repelling or killing pests (such as moths), however, is an indication that they might not be safe as bedding for animals.
Chemicals responsible for the "good" properties of wood beddings also cause:
- Respiratory tract damage and disease
- Liver damage and disease
Pine and cedar, and products derived from them, are used by humans for a number of applications as well. Therefore, hazards associated with contact of softwoods are also a human health concern.
The toxic chemicals found in softwoods are aromatic (volatile) hydrocarbons. The primary irritant in cedar is plicatic acid, and the primary irritant in pine is abietic acid. Plicatic acid is most concentrated in western red cedar (Thuja plicata), but is also found in significant quantities in eastern white cedar (Thuja occidentalis) and Japanese cedar (Cryptomeria japonica). Abietic acid is found in varying quantities in all pine trees (family Pinaceae) and is the main component of colophony (rosin) which is a derivative of pine trees with a number of industrial applications (Johnston 1995).
EFFECTS OF SOFTWOODS ON
RESPIRATORY PHYSIOLOGY AND FUNCTION
Plicatic acid (PA) has been identified as the primary irritant in cedar in a number of studies. Much of the research performed on PA has been with sawmill workers because of the relatively high rate of western red cedar asthma (WRCA) in the sawmill industry. In 1989, Chan-Yeung et al. measured histamine and leukotriene E4 (LTE4) levels in bronchial fluid of subjects exposed to PA. Workers with WRCA, atopic asthma, and no asthma were tested. PA only induced a significant increase in histamine and LTE4 levels in the WRCA patients meaning that the WRCA patients were the only subjects sensitized to PA and PA is the specific cause of their allergic reaction (Chan-Yeung et al. 1989) (Fig. 1). Similarly, Frew et al. (1993) found that PA caused release of histamine from bronchial mast cells in WRCA patients, but not in patients with atopic asthma. It has also been shown that sawmill workers with WRCA do not have an allergic response to a WRC extract if the PA has been chemically extracted (Chan-Yeung 1994).
Evidence that Plicatic Acid is the Primary Irritant in Cedar
Effects of Plicatic Acid
- Human StudiesWestern red cedar asthma affects between 4 and 13.5% of exposed populations, such as sawmill workers (Chan-Yeung 1994). Eastern white cedar (EWC) has identical effects, but is only half as potent as western red cedar (WRC) because it contains only half as much PA. WRCA and EWCA patients show cross-reactivity with both cedar species which affirms that PA is the causal agent in both cases (Cartier et al.1986).
The effects of PA are similar to other inflammatory an allergic reactions. PA induces the release of immunoglobulins , histamine, and leukotrienes, and causes an increase of eosinophil and T-cell levels in the blood. PA can cause both Type-I hypersensitivity, an immediate increase in immunoglobulin E (IgE), and Type-IV hypersensitivity, a delayed effect, of the respiratory system. WRCA patients may exhibit either or both types (Johnston 1985).
In studies where WRCA patients have been removed from exposure to WRC, and therefore PA, less that 50% of cases resolve (Choubrac 1991 and Rosenberg 1989). Similarly, in a study of 136 sawmill workers with WRCA, 60% continued to have frequent asthma attacks after a year away from work (Chan-Yeung 1987). Although eliminating exposure to PA does not guarantee a restoration of health, after a year of medical treatment, no WRCA patients recovered when continuing to work in a sawmill (Cote 1990). In the same study, 10% showed any improvement, 62% remained stable, and 38% showed a decline in condition (Cote 1990). The finding that the disease does not resolve after exposure to PA is eliminated means that definite physiological changes have occurred, such as in the function of the immune and respiratory systems.
- Animal StudiesA comprehensive study using guinea pigs (Cavia porcellus) by Salari et al. (1994) provides additional evidence regarding the immune-mediated allergic response to PA. Guinea pigs were sensitized to PA over a period of six months via bi-weekly injections of PA. After three months, PA-specific immunoglobulin G1 (IgG1) antibodies were detected. After the six month injection period, assays were performed to access the effects of PA with the following results:
(1) Lung mast cells and blood basophils released histamine, LTD4, and prostaglandin D2 (PGD2) in response to PA in vitro
(2) Harvested tracheal tissue contracted upon exposure to PA
(3) Untreated guinea pig tracheal tissue could be passively sensitized with serum from PA-sensitized subjects and would contract in response to PA
(4) Untreated guinea pig tracheal tissue passively sensitized with immunoglobulin-free serum from PA-sensitized subjects did not contract in response to PA
These findings show that: (1) the response to PA is immune-mediated and similar in nature to other allergic/inflammatory reactions, (2) PA is the sensitizing irritant causing asthmatic constriction in tracheal tissue, (3) the mediator responsible for eliciting a reaction to PA is contained in blood serum, and (4) the mediator responsible is an immunoglobulin. These findings agree with a human study by Vedal et al. (1986) where PA-specific IgE was associated with nonspecific bronchial hyper- responsiveness (analogous to contraction in Salari et al. 1994).
Ayers et al. (1989) presents another comprehensive study, but where the effects of PA and abietic acid (AA) were both examined. Monolayers of rat type II and human A549 alveolar epithelial cells, intact rat lungs, and rat tracheal explants were exposed to several concentrations of PA and AA. Both PA and AA caused time and dose dependent lysis of rat and human alveolar epithelial cells (Fig. 2). When PA and AA were injected into intact rat lungs, sloughing of bronchial epithelial cells was observed upon examination of harvested organs. There was also time and dose dependent sloughing of epithelial cells in tracheal explants (Fig. 3). These findings show that PA and AA are cytotoxic and damage alveolar, tracheal, and bronchial epithelial tissue of the respiratory tract and therefore support that exposure to PA and AA via cedar and pine is a major occupational hazard and neither is acceptable for use as an animal bedding.
As discussed, Ayars et al. (1989) presents data identifying AA as the primary irritant in pine. Like PA, AA caused time/dose dependent lysis of rat and human alveolar cells (Fig. 2), sloughing of bronchial epithelial tissue in intact rat lungs, and time/dose dependent sloughing of rat explant epithelial tracheal tissue (Fig. 3). In addition, AA also caused sloughing of the alveolar epithelium in intact rat lungs. In this study, the effects of AA were more pronounced; AA seemed to have a higher potency than PA which is inconsistent with other studies where PA is identified as a more toxic agent. The greater effect of AA in this study in the result of AA and PA being tested at identical concentrations. In most other studies, PA and AA extracts have been prepared from wood samples and because AA is naturally present at much lower concentrations in pine than PA is in cedar, the pine extracts are less concentrated as well.
Evidence that Abietic Acid is the Primarily Irritant in Pine
Effects of Abietic Acid
- Human StudiesAbietic acid is found in colophony, a derivative of pine trees also called rosin. Colophony has a number of industrial applications including solder fluxes, paper sizing, adhesives, paints, varnishes, printing inks, and plasticizers (Sadhra et al. 1994). The composition of colophony is 90% resin acids and 10% component esters, aldehydes, and alcohols. The resin acids are all isomers of AA (heat and oxygen can cause isomerization). As it contains abietic acid, colophony is a major occupational health hazard and is the third highest cause of occupational asthma. In the Guinea Pig Maximization Skin Sensitivity Test, colophony is rated grade IV (strong), but AA is rated III (moderate). This result led to the finding that it is the oxidized form of abietic acid (15-hydroperoxyabietic acid) that is the most active form. This finding is supported by the fact that hydrogenation (reduction) of colophony gives it the same activity as pure AA (Sadhra et al. 1994).
- Animal StudiesFar less research has been conducted regarding the respiratory effects of AA than of PA; however, all the studies that have been performed show that it is also a major health hazard (Ayars et al. 1989; Sadhra et al. 1994). Odynets et al. (1991) performed a detailed study comparing pine, spruce, birch, aspen, and cellulose (control). In a toxicity screen using Tetrahymena pyriformis, all woods inhibited growth in comparison to cellulose, but pine inhibited growth to the greatest degree (Fig. 4). Odynets et al. (1991) also performed a number of experiments with mice:
- Immune Response
After being housed on a specific bedding for one month, Icr:Icl mice were immunized with sheep erythrocytes and spleens were then examined for plaque forming cells (PFC) after five days by addition of T-dependent antigen. Only mice housed on pine bedding showed a PFC count significantly higher (p = 0.05) than the control group kept on cellulose bedding (Fig. 5).
- Relative Liver Mass
C57BL/6 and BALB/c mice were housed on a specific bedding from birth. At 8 months, livers were collected and massed. Pine was the only bedding that caused a significant increase (p = 0.05) in liver mass (compared to cellulose group) in male and female groups of both breeds (Fig. 6).
- Evaluation of Reproductive Activity
C57BL/6 and BALB/c mice were housed on a specific bedding from birth. K1 was devised as an index of reproductive rate, and K2 as an index of reproductive productivity.
K1 = # offspring weaned from female's first litter
period from female's birth to weaning of first litter
K2 = # offspring weaned from five litters of one female
period from female's birth to weaning of five litters
Females of both breeds housed on pine showed a significantly (p = 0.05) lower a K1 and K2 than females house on aspen (Fig. 7).
- Evaluation of Bedding Choice
C57BL/6, BALB/c, and wild mice were placed in modified cages with a choice of bedding (pine, spruce, birch, aspen). All mice significantly preferred aspen (p = 0.05), and no mice chose pine (Fig. 8).
These results show that pine does have a number of adverse physiological effects. In addition, mice actually preferred the bedding that was least toxic, elicited the lowest immune response, had the least effect on the liver, and gave the highest reproductive capabilities.
EFFECTS OF SOFTWOODS ON
LIVER PHYSIOLOGY AND FUNCTION
- Human StudiesThe effects of pine and cedar on human liver function has not been studied, but the fact that small mammals, such as mice, rats, guinea pigs, and rabbits, all show the same adverse liver reactions makes pine and cedar of direct concern to humans. Animal testing is always meant to gain knowledge regarding the function of the animal being studied, but is also usually meant to serve as a model for a human reaction. Extensive testing has shown that liver function of small mammals is similar to that of humans, and therefore it can be inferred that the same liver effects seen in small mammals are likely to occur in humans (TeSelle, 1993). Because humans are not forced to live directly in softwood shavings the risk is reduced, however, the subject deserves study.
- Animal StudiesIn one of the first studies regarding the effects of softwood beddings on liver function, Vessel (1967) found that use of softwood beddings did significantly increase the production of three liver microsomal enzymes. The study was spurred by the discovery of an immediate decrease in Evipal (hexobarbital) sleeping time after the introduction of softwood bedding in a previous study. The factor responsible was not initially known because bedding, cage type, and food had all been changed simultaneously; however, each factor was examined independently and the softwood bedding was identified as the cause.
Vessel (1967) carried out experiments with a number of strains of mice and rats. In every case, sleeping time was defined as the time period from intraperitoneal (IP) injection to the point of righting-response restoration. At the restoration of righting-response, both livers and brains were harvested for further study. Brain preparations were used to verify that the same concentration of hexobarbital was present in animals with a decreased sleeping time and normal sleeping time. Liver preparations were assayed for enzyme activity. Enzyme activities (hexobarbital oxidase, aniline hydroxylase, and ethyl morphine N-demethylase) were all significantly higher for animals housed on softwood beddings (Fig. 9). When animals housed previously on softwoods were moved to a hardwood bedding, sleeping time and liver enzyme activity returned to normal levels (Fig. 10).
The results of Vessel's experiments identified a time dependent effect on both sleeping time and activity of liver enzymes as well as a correlation between the two:
- 24-hours post placement on WRC bedding mouse sleeping time decreased by 33% and liver enzyme activity increased by 33%
- 48-hours post placement on WRC bedding mouse sleeping time decreased by 66% and liver enzyme activity increased by 66%
Experiments were replicated with white pine and ponderosa pine beddings and similar results were observed. Interestingly, the toxic effects of softwood beddings can be reduced with heat treatment and chemical extraction of aromatic compounds:
- Mice housed on hexane-extracted and autoclaved WRC bedding for eight days showed a 25% decrease in sleeping time as opposed to the 80% decrease in mice housed on untreated bedding for the same time period (Vessel 1967).
Since the time of publication of Vessel's study, the effects of aromatic hydrocarbons in softwoods on liver function has been studied in detail. It has been established, as in respiratory irritation, that the active irritants in cedar and pine are PA and AA respectively (Törrönen et al. 1989). In a comprehensive experiment by Törrönen et al. (1989), in vivo and in vitro studies were performed with rats and mice to test differences between softwood, hardwood, and inert cellulose bedding materials.
- In vivo experiment
Rats were housed without bedding for two weeks, and then moved to:
- softwood bedding: pine (Pinus silvestrus)
- hardwood bedding: alder (Alnus incana) or aspen (Populus tremula)
- no bedding: control
for an additional two weeks prior to harvesting of livers. Although eight liver enzyme levels were assayed, a significant increase in activity (indicating a change in liver function) was only seen for aldehyde dehydrogenase in the pine and alder groups.
- In vitro experiment
The mouse hepatoma cell-line, Hepa-1, was used in order to design a more controlled study of the beddings. Cell cultures were exposed to acetone extracts of:
- softwood bedding: pine (Pinus silvestrus) or pine/spruce (Picea abies)
- hardwood bedding: alder (Alnus incana) or aspen (Populus tremula)
- inert bedding: cellulose material (control)
In assays for cytotoxicity and induction of liver enzyme production (aryl hydrocarbon hydroxylase and aldehyde dehydrogenase), softwoods produced a much stronger effect.
The fact that hardwood (aspen and alder) extracts also showed a degree of cytotoxicity and liver enzyme induction means that they too should be avoided as bedding materials.
Although cedar and pine have been eliminated from laboratories and ongoing research continues to understand their harmful effects, both materials continue to be used as bedding for companion animals. The Guide for the Care and Use of Laboratory Animals (1996), an official guide released by the National Research Council, explicitly states that softwood beddings have been shown to induce liver microsomal enzyme production, increase incidence of cancer, and are cytotoxic. Pine and cedar beddings continue to be available because consumers are misinformed, a result of ignorance and lack of concern in the pet industry. Many organizations have become aware of the dangers of softwood bedding and now work to publicize the associated dangers. For example, the House Rabbit Society, a nation-wide organization that harbors abandoned rabbits and promotes their proper care, was one of the first companion animal groups to recognize the harmful effects of softwood beddings. In an informal study in 1989, the HRS determined that otherwise healthy rabbits, if housed on pine or cedar bedding, showed elevated liver enzymes in blood tests, and showed a higher rate of liver disease and cancer (Harriman 1989). They also found that the rabbits, if moved to inert bedding materials, showed normal liver enzyme levels after one month (Harriman 1989).
Softwood beddings are generally less expensive than safer alternatives, and, ironically, the aromatic hydrocarbons making them dangerous also make them attractive in terms of deodorization. The new generation of veterinarians specializing in exotic animals (which includes the small mammals), animal advocacy groups, and better distribution of information to pet owners through pet stores are all helping to stop the use of pine and cedar as companion animal beddings.
CHEMICALS IN SOFTWOODS
In a 1974 publication, Schoental (1974) studied two aromatic hydrocarbons, coniferaldehyde and sinapaldehyde, found in pine and cedar respectively. Both compounds are normal constituents of wood lignin and can be isolated by thin layer liquid chromatography. Schoental found that both compounds, and particularly sinapaldehyde, readily isomerize and undergo redox reactions to produce carcinogenic compounds. For example, 3,4,5-trimethoxycinnamaldehyde (TMCA), the p-O-methyl derivative of sinapaldehyde, was shown to cause many types of tumors in rats, including squamous-cell carcinomas. An oxidation product of sinapaldehyde present in wood, 2, 6-dimethoxy-1,4-benzoquinone, was shown to induce sarcomas in rats following subcutaneous injection. The presence of additional hazardous chemicals in softwoods gives even greater reason to avoid them as bedding materials for companion animals.
FOR COMPANION ANIMALS
As is evidenced in the studies described, no wood bedding is without risk, although hardwoods, such as aspen, are highly preferable to softwoods. A number of safer alternative beddings are available for companion animals. In choosing an appropriate bedding for companion animals, consider the particularly needs of your animal.
| - Pelleted recycled
- Pelleted organic materials
- Shredded newsprint
| - Wire floor
- Pelleted litters
- Straw or hay
- Ground corn-cob
- Shredded newsprint
- Old cotton clothing
|The House Rabbit Society
Oxbow Hay Company
1996. Warning About Pine and Cedar Bedding. Todd's Guinea Pig Hutch.
(21 Sept. 1999)
Guide to the Care and Use of Laboratory Animals, 1st ed. 1996. U.S. Dept. of Health and Human Services.
Ayars, G.H., L.C. Altman, C.E. Frazier, and E.Y. Chi. 1989. The toxicity of constituents of cedar and pine woods to pulmonary epithelium. The Journal of Allergy and Clinical Immunology 83:610-8.
Cartier, A., H. Chan, J-L Malo, L. Pineau, K.S. Tse, and M. Chan-Yeung. 1986. Occupational asthma caused by eastern white cedar (Thuja occidentalis) with demonstration that plicatic acid is persent in this wood dust and is the causal agent. The Journal of Allergy and Clinical Immunology 77:610+639-45.
Cartier, A., R.T. Jocelyne L'Archevêque, and J-L Malo. 1986. Exposure to a sensitizing occupational agent can cause a long-lasting increase in bronchial repsonsiveness to histamine in the absence of signigicant changes in airway caliber. The Journal of Allergy and Clinical Immunology 78:1185-9.
Chan-Yeung, M., H. Chan, K.S. Tse, H. Salari, and S. Lam. 1989. Histamine and leukotrienes release in brochoalveolar fluid during plicatic acid-induced bronchoconstriction. The Journal of Allergy and Clinical Immunology 85:762-8.
Chan-Yeung, M. 1994. Mechanism of occupational asthma due to western red cedar (Thuja plicata). American Journal of Industrial Medicine 25:13-8.
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Harriman, M. 1989. Litterboxes and Liver Disease. Hourse Rabbit Hournal: Litterboxes and Liver Disease.
(21 Nov. 1999)
Johnston, Jeff. 1995. Respiratory Toxicity of Cedar and Pine Wood: A review of the bimedical literature from 1986 through 1995.
(21 Sept. 1999)
Odynets, A., O. Simonova, A. Kozhuhov, T. Saitsev, A. Verreva, L. Gnilomedova, and R. Rudzish. 1991. Beddings for laboratory animals: Criteria of Biological evaluation. Laboratornye Zhyvotnye 1:70-6.
Rocke, Emily. Safe Pet Bedding FAQ.
(21 Sept. 1999)
Sadhra, S., I.S. Foulds, C.N. Gray, D. Koh, and K. Gardiner. 1994. Colophony: Uses, health effects, airborne measurement and analysis. The Annals of Occupational Hygiene 38:385-96.
Salari, H., S. Howard, H. Chan, P. Dryden, and M. Chan-Yeung. 1994. Involvement of immunologic mechanisms in a guinea pig model of western red cedar asthma. The Journal of Clinical Immunology 93:877-84.
Schoental, R. 1973. Carcinogenicity of wood shavings. Laboratory Animals 7:47-9.
TeSelle, E.R. 1993. The Problem with Pine: A discussion of softwood beddings. AFRMA-Cedar & Pine/Cage Hygeine.
(20 Nov. 1999)
Törrönen, R., K. Pelkonen, and S. Kärenlampi. 1989. Enzyme-inducing and cytotoxic effects of wood-based materials used as bedding for laboratory animals: Comparison by cell culture study. Life Sciences 45:559-65.
Vedal, S., M. Chan-Yeung, D. A. Enarson, J. Chan, E. Dorken, and K.S. Tse. 1986. Plicatic acid-specific IgE and nonspecific bronchial hyperresponsiveness in western red cedar workers. The Journal of Allergy and Clinical Immunology 78:1103-9.
Vessel, E.S. 1967. Induction of drup-metabolizing enzymes in liver microsomes of mice and rats by softwood bedding. Science 157:1057-8.
Wagner, R. Kelly. 1999. "What's the Scoop: What's wrong with cedar shavings?" Why You Should Not Use Cedar Shavings as Pet Bedding.
(21 Sept. 1999)
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Introduction Effects of Softwoods on Respiratory Physiology and Function Effects of Softwoods on Liver Physiology and Function Additional Harmful Chemicals in Softwoods Alternative Beddings for Companion Animals References Please send questions or comments regarding this website to Nathaniel Cook.