We pride ourselves in that we give customers another choice, a safer alternative,  rather than one with long term risks  in comparison to systemic risky topical flea treatments and DEET products.

If there is any concern about Phenols in our products, let us reassure you when the cedar oil is extracted from the cedar tree it is screened, tested, refined and purified. It is then further diluted with 100% distilled water for the cedar oil, you won’t find that process anywhere else, so that it stays in liquid form, no additives or chemicals are added, any more pure it would be in a petrified state, the cedar oil is further blended with the natural ingredients for our pet shampoo. Overall, our drinking water has more phenol than any trace amount, parts per millions per millions, if there were, in our products.

NOTE:  MISUSE OF THIS PRODUCT MAY CAUSE PEOPLE AND  ANIMALS TO COUGH. PLEASE READ THE SAFETY INFORMATION ABOUT CEDAR OIL BELOW AND FOLLOW THE APPLICATION INSTRUCTIONS.

CEDAR OIL  IS NOT TO BE SPRAYED ON CATS NEITHER DIRECTLY OR INDIRECTLY (meaning not even applying with a cloth). Cedar Oil Pet Shampoo is to be used on cat’s exclusively, the cedar oil spray is ONLY  to be used to treat their bedding and areas where they sleep and our carpet shampoo used to treat the home in which they live. 

NOTE:  Even though our products are 100 % natural and environmentally safe, and although allergic reactions are rare, it is NOT recommended for use on very small pets such as: Hamsters, Gerbils, Rodents, Guinea Pigs, Spiders, Tarantulas, Snakes and many other small animals.  For these small animals, consult your veterinarian for more appropriate methods.  Only to be used on humans, horses, cattle, and dogs (older than 6 months of age).

ALTHOUGH ALLERGIC REACTIONS ARE RARE, WE RECOMMEND THAT YOU SPRAY A VERY SMALL AMOUNT OF THE CEDAR OIL ON A CLOTH AND APPLY IT TO A SMALL AREA OF YOUR PET, PREFERABLY AWAY FROM THE NOSE AND MOUTH, TO TEST FOR A REACTION.

 

Safety Study

SUMMARY OF DATA FOR CHEMICAL SELECTION

Cedarwood Oil
8000-27-9

BASIS OF NOMINATION TO THE CSWG

Cedarwood oil is brought to the attention of the Chemical Selection Working Group (CSWG) as the active component of widely used insect repellants.

Three distinct  cedarwood  oil  products,  Virginia  cedarwood  oil,  Texas  cedarwood  oil,  and Western red cedar (Thuja plicata) oil, can be identified.  The common major ingredients in the Virginia and Texas oils are cedrol, -cedrene, and thujopsene, but the relative percentages vary depending on the origin of the cedar trees  used to produce the oil. Western cedarwood oil contains methyl thujate and thujic acid.

Virginia cedarwood  oil  is  widely  used  as  a  fragrance  in  soaps,  air  fresheners,  household detergents, and cosmetics.  The National Institute for Occupational Safety and Health (NIOSH) estimated that nearly 118 thousand workers are potentially exposed to Virginia cedarwood oil based on data collected in the 1980s. It is also the active ingredient in cedar balls/wood blocks used  as  moth  repellants  and  in  bug  blocks.    Because  of  concerns  about  the  toxicity  of naphthalene (“moth balls”) and high concentrations of Deet (active ingedient  in many bug blocks), the market for cedarwood oil products is expected to grow.

Although cedarwood oil has been described as a powerful abortifacient, very little data on the toxicity of any  of the three cedarwood oils was found in a review of the available literature. Cedar shavings used as bedding have been reported to stimulate drug-metabolizing enzymes in rodents and affect the mortality of rat pups.

SELECTION STATUS

ACTION BY CSWG:  June 20, 2002

Studies requested:

– Subchronic study (90 day) of Virginia cedarwood oil

Priority: Moderate

Rationale/Remarks:

– Widespread exposure to Virginia cedarwood oil even though production volumes are greater for Texas cedarwood oil, which has greater usage as a chemical intermediate.

– Potential substitute for naphthalene moth balls

– Lack of basic toxicology data on this product

-Reregistration eligibility has already been determined by EPA; additional toxicological data will not become available through this avenue.

INPUT FROM GOVERNMENT AGENCIES/INDUSTRY

Dr. Esther Rinde from the US Environmental Protection Agency (EPA) provided information on the status of testing required by the Reregistration Eligibility Decision (RED) for cedarwood oil.

Cedarwood Oil
8000-27-9

CHEMICAL IDENTIFICATION

Cedarwood oils are extracted from several members of the family Cupressaceae, which includes true  cedars, junipers, and cypresses.    In the US, cedarwood oil is harvested mainly from Juniperus virginiana (Eastern red cedar or Virginia cedar), Juniperus ashei or mexicana (Texas cedar), and Thuja plicata (Western red cedar).  According to the Food and Agriculture Organization of the United Nations (FAO), Western red cedar is the least used of the three (FAO, 1995a & 1995b).

Cedarwood oil, Virginia

CAS Registry Number:    8000-27-9

Chemical Abstracts Service Name:    Cedarwood   oil,   Virginiana   (Allured   FFM,   1999; ChemID,   2002).   CAS   registry   number   also applied  to  Chinese  cedarwood  oil    (Cupressus funebris),  Kenyan or East African cedarwood oil (Juniperus   procea),   and   Moroccan   or   Atlas cedarwood    oil    (Cedrus  atlantica)  (ChemID,
2002; FAO, 1995a)

Synonyms and Trade Names:    Cedar oil; cedarwood oil; red cedarwood oil; EPA Pesticide    Chemical    Code    040505    (ChemID,
2002)

Chemical and Physical Properties:

Description:    Light   yellow   to   pale   brown   viscous   liquid; sometimes solidifies at room temperature; cedar odor (Gerhartz, 1988)

Density:    d25 0.939-0.958 (Gerhartz, 1988) Solubility:    Soluble in ethanol (Gerhartz, 1988)

Texas Cedarwood oil

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CAS Registry Number:    68990-83-0

Chemical Abstracts Service Name:        Texas    cedarwood    oil    (Allured    FFM,    1999; ChemID, 2002)

Synonyms and Trade Names:    Texan cedarwood oil (ChemID, 2002)

Chemical and Physical Properties:

Description:    Brown  to  reddish-brown,  viscous  liquid;  may partially   solidify  at  room  temperature;  cedar odor(Gerhartz, 1988)
Density:    d20 0.954-0.967 (Gerhartz, 1988) Solubility:    Soluble in ethanol (Gerhartz, 1988)

Western red cedar oil

CAS Registry Number:    68917-35-1

Chemical Abstracts Service Name:    Thuja plicata oil (STNEasy, 2002)

Synonyms and Trade Names:    Western red cedarwood oil (Laurel Laboratories, Inc., 2002)

Cedarwood oil components:  The composition of cedarwood oils varies depending on the source.  Cedrol and thujopsene are the major components of Texas and Virginia oils; Virginia oils also contain significant quantities of -cedrene (Mookherjee & Wilson, 1996). The volatile oil from Western juniper has been reported to contain 15-40% cedrol (Kurth & Ross, 1954). Methyl thujate and thujic acid are the primary ingredients found in Western
red cedarwood oil (Laurel Laboratories, Inc., 2002). The principal constituents of

cedarwood oils are shown in Table 1.

Table 2 summarizes the chemical and physical properties of the major components of

Virginia and Texas cedarwood oils.
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Table 1. Chemical Composition of Cedarwood Oils

Component    CAS No.    Texas Oil (%)    Virginia Oil (%)    Western Red
Cedarwood Oil (%)
Thujopsene    470-40-6    60.4    27.6    –
Cedrol    77-53-2    19.0    15.8    –
∀-Cedrene    469-61-4    1.8    27.2    –
∃-Cedrene    546-58-1    1.6    7.7    –
∀-Copaene    3856-25-5    2.8    6.3    –
Widdrol    6892-80-4    1.1    1.0    –
Methyl thujate        –    –    65
Thujic acid        –    –    25
∃-Thujaplicin    499-44-5    –    –    1
∀-Thujaplicin        –    –    1
Source: Lawrence, 1993; Laurel Laboratories, Inc., 2002; Mookherjee & Wilson, 1996

Technical Products and Impurities:  The composition of cedarwood oils is complex and varies depending on the  species of trees used in the extraction process.    The International Organization for Standardization (ISO) and the Fragrance Manufacturers Association (FMA) provides  standards for Texas and Virginia cedarwood oils.   The ISO standard specifies an alcohol content  (expressed as cedrol) of 35-48% with a minimum cedrol content of 20% for Texas cedarwood oil.  For Virginia oil, a maximum cedrol content of
14% is specified.    Compositional data for American oils, as specified by the FMA

standards are  somewhat  different.  The  FMA  standard  specifies  the  alcohol  content

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(cedrol and related isomers) for Texas oils as 25-42% and for Virginia oils as 18-38% (FAO, 1995a).

Chinese and Cedrus atlanticus cedarwood oil imports are also commercially available (AromaWeb,  2001; Schreiber, 1996). Chinese cedarwood oil from Cupressus funebris, which is widely used in the US, has a composition very similar to Texas cedarwood oil (Gerhartz, 1988; Schreiber, 1996).  The FMA requires an 8% minimum alcohol content for Chinese cedarwood oil (FAO, 1995a).

Table 2. Chemical and Physical Properties of Major Components of Virginia and Texas Cedarwood Oils

Component    Synonyms    Chemical and Physical
Properties/Percentage in oil
Cedrol [CAS No. 77-53-2]

H3C    OH CH3

H3C   CH3

Mol. Wt.: 222.37
C15H26O    (+)-Cedrol
(ChemID,
2002)    Crystalline solid, needles from dil. methanol
(Merck, 2001; Sigma-Aldrich, 2002a)

Melting Point: 86-87 C (Merck, 2001)

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Thujopsene [CAS No. 470-40-6]

H 3C    CH 3
CH 3

CH 3

Mol. Wt.: 204.35
C15H24    (-)-Thujopsene, widdrene (ChemID, 2002)    Colorless, clear liquid (Merck, 2001; Sigma- Aldrich, 2002a)

Boiling Point: 120C (Merck, 2001); 258-
260 C (Sigma-Aldrich, 2002a)
Flash Point: 104C (Sigma-Aldrich, 2002a) Solubility: Insoluble in water, soluble in common organic solvents (Sigma-Aldrich,
2002a)
∀-Cedrene [CAS No. 469-61-4]

H3C     CH3

H3C     CH3

Mol. Wt.: 204.36
C15H24    Cedr-8-ene, (ChemID,
2002)    Colorless, clear liquid (Sigma-Aldrich,
2002a)

Boiling Point: 261-262C (Sigma-Aldrich,
2002a)
Flash Point: 104C (Sigma-Aldrich, 2002a) Solubility: Insoluble in water, soluble in benzene (Sigma-Aldrich, 2002a)

Virginia cedarwood oil [CAS No. 8000-27-9], Texas cedarwood oil [CAS No. 68990-83-0], (+)-cedrol (99.0 %) [CAS No. 77-53-2], (-)-thujopsene (97.0 %) [CAS No. 470-40-6], (-
)--cedrene (99.0 %) [CAS No. 469-61-4], (+)- -cedrene (~97 %) [CAS No.  546-28-1],

(-)--copaene (~95 %) [CAS No. 3856-25-5], and -thujaplicin (99%) [CAS No. 499-44-5]

are available from Sigma-Aldrich (Sigma-Aldrich, 2002b).

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EXPOSURE INFORMATION Production and Producers:
Manufacturing Process:    Virginia cedarwood oil is produced by steam distillation of sawdust, finely chipped waste wood from the manufacture of cedarwood products, or from stumps and logs of   Juniperus virginiana.  Texas cedarwood oil is obtained by steam distillation of chopped wood from   Juniperus ashei or Juniperus mexicana. Although the most popular method for precessing  cedarwood for oil production is steam distillation, some cedarwood oils are also produced through solvent extraction (Australian National University, 1999; Gerhartz, 1988; Schreiber, 1996).

Producers and Importers:   Thirteen US producers or distributors of cedarwood oil are listed by Chemical Sources International (2002).

According to recent issues of chemical directories, cedarwood oil is manufactured and/or  distributed by Berje Inc.; Brutanicals, Inc.; The Lebermuth Co., Inc.; Penta Manufacturing  Co.;  Polarome  International,  Inc.;  Ruger  Chemical  Co.,  Inc.;  and Spectrum Chemical MFG Corp. (Hunter, 2001; Tilton, 2001).

Production/Import/Export Level:  Virginia and Texas cedarwood oils, Thuja plicata oil, cedrol, -cedrene, and thujopsene are listed in the EPA Toxic Substances Control Act (TSCA) Inventory (ChemID, 2002).

The Port Import/Export Reporting Service (PIERS) reported cedarwood oil imports with a cargo weight of 23,302 pounds over the 11 month period from April 3, 2001 to February 20, 2002.  For the 18-month period between September 12, 2000 and March
16, 2002, PIERS reported cedarwood oil exports with a cargo weight of 96,012 pounds (Dialog Information Services, 2002a, 2002b).

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Use Pattern:  The US production of cedarwood oil in 1984 was reported to be 1,400 tons for the Texas oil and  240 tons for the Virginia oil (FAO, 1995b). The production of cedarwood oil is expected to rise because of government incentive programs for the use of red cedar trees (Adams, 1987; Oklahoma State University, 2001).

Although Texas cedarwood oil is produced in larger quantities than cedarwood oil from  the  Eastern  cedar  (Juniperus  virginiana),  it  is  used  almost  exclusively  as feedstock for the manufacture of chemical derivatives, such as cedrol, cedryl methyl ether, acetyl cedrene, and cedryl acetate. Imports of Chinese cedarwood oil are also used to produce these derivatives.  In contrast, Virginia cedarwood oil is widely used in the fragrance industry, among others (FAO, 1995b;  Gerhartz, 1988; Schreiber,
1996).

Virginia cedarwood oils have many commercial uses.  They are used to restore the smell of  cedar  to furniture and in cosmetic formulations, including shampoos for humans and animals, aftershave lotions, soap bars, and perfumes. They are also found in insect repellents, massage oils, incense oils, and shavings used as bedding for small animals. Thuja plicata or Cedrus atlantica cedarwood oils may also be used in some of these products (Absorbine Jr., 2002; Adams, 1987; Australian National University,
1999; Aroma-essence.com, 2002; Cedarcide, 2002; Country Cottage Works, 2002; Drugstore.com,  2002; FAO, 1995b; Frontier Natural Products Co-op, 2002; Lady Lorelei,  2002;  POCO,  LLC,  2002;  Resource  Management  Group,  2002;  Sawyer,
2002; Skeeter Defeater, 2002).

Cedarwood oil alcohols and terpenes are food additives considered by the US Food and Drug Administration (FDA) to be Generally Recognized as Safe (GRAS).  These

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food additives are used as flavor enhancers, flavoring agents, or adjuvants.  Food use of cedarwood oil terpenes was estimated to be 166,666 lb in 1987 (EPA, 1993; FDA,
2002; Clydesdale, 1997).

Cedarwood oil and thickened cedarwood oil have laboratory uses as immersion oils for light microscopy and for clearing microscope sections (Baker’s Chemicals, 2002; PolySciences, Inc., 2001; Sigma-Aldrich, 2002b).

Cedarwood oil, in combination with other products, is used as a homeopathic remedy and is sold as a vaporizing ointment for topical use (Health Canada, 2002).

A total of 349 patents using cedarwood oil were on file with the US Patent and

Trademark Office (USPTO) as of May 2002 (US Patents and Trademark Office,

2002).

Human Exposure:

Occupational Exposure: The National Occupational Exposure Survey (NOES), which was conducted by the National Institute for Occupational Safety and Health (NIOSH) between  1981  and  1983,   estimated  that  117,858  workers  in  7,990  facilities representing 67 industries were potentially exposed to Virginia cedarwood oil in the workplace.  The NOES database does not contain information on the frequency, level, or duration of exposure to workers of any chemical listed  therein  (Sigma-Aldrich,
2002a).

Cedarwood oil exposure may also occur in laboratories as a result of its use as immersion oil (PolySciences, 2001).

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Environmental Exposure:  -Cedrene, a constituent of cedarwood oil, has been found in chemical  wastes in the water of the Great Lakes. The sources of -cedrene may derive from natural plant products or pulp mills (Passino-Reader et al., 1997).

Consumer Exposure:  The largest number of human exposures to cedarwood oil occurs among consumers using insecticide products, deodorants, soaps, air fresheners, floor polishes,   and   sanitation   supplies   containing   cedarwood   oil.    Consumers   are potentially exposed to cedarwood oil through inhalation and dermal contact.

Although registration as a pesticide is no longer required by EPA for cedarwood oil, several   formulations  have  been  registered  as  pesticides  in  the  past.    These formulations include: ready-to-use liquids containing 0.48% cedarwood oil, wood blocks  containing  2-8% cedarwood oil, and pet collars with 0.5% cedarwood oil (EPA, 1993).  Two pesticides, Bug Block sunscreen and insect repellent, containing
0.46% Texas cedarwood oil, and Nexa cedarwood oil moth protection, containing

40% Virginia cedarwood oil, are registered with the state of California as pesticides

(California EPA, 2001).

Two typical products for human topical use, Cedarcide (2002) and Skeeter Defeater

(2002) contain 1 and 5% cedarwood oil, respectively.

Environmental  Occurrence:  Cedarwood  oil  contains  natural  products  found  in  cedar, juniper, and cypress woods and steam distillation derivatives of such products.

Regulatory Status: No standards or guidelines have been set by NIOSH or the Occupational Safety and Health Administration (OSHA) for occupational exposure to or workplace allowable levels of cedarwood  oil.  Cedarwood oil is not listed on the American

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Conference of Governmental Industrial Hygienists (ACGIH) list of compounds for which recommendations for a Threshold Limit Value (TLV) or Biological Exposure Index (BEI) are made.

Cedarwood oil was initially registered in 1960 as a pesticide to repel moths from clothing. As  such, cedarwood oil was subject to the requirements for reregistration eligibility promulgated in  1988.   EPA issued its Reregistration Eligibility Decision (RED) document for cedarwood oil in 1993.  The RED profiles the use of cedarwood oil as a natural repellant/feeding depressant and fungicide used in houses and on pets or their bedding to repel fleas, moths, and mildew.  Based on information collected as the result of the RED, EPA deregulated cedarwood oil in 1996 and no longer requires manufacturers of cedarwood oil products to register them as pesticides (EPA, 1993; Rinde, 2002).

Cedarwood oil is not listed as a hazardous substance, priority pollutant, or toxic pollutant under the Clean Water Act.

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EVIDENCE FOR POSSIBLE CARCINOGENIC ACTIVITY

Human Data: No epidemiological studies or case reports investigating the association of exposure to cedarwood oil and cancer risks in humans were identified in the available literature.

Reports  describing  cedarwood  oils  as  irritants  or  sensitizers  appear  to  be  rare (Botanical   Dermatology  Database,  2001).  Cedarwood  oil  (no  origin  specified) produced no response in  humans after 48 h when administered as a patch test at a concentration  of  8%  in  petrolatum  (HSDB,  2002).  The  Danish  Environmental Protection Agency (2002) classified cedarwood oil used in household and cosmetic detergents as a rare sensitizer fragrance based on the results of  patch tests on patients with cosmetic dermatitis and controls.

Historically, nineteenth  century  medical  compendiums  contain  several  reports  of abortion and death in humans after oral consumption of relatively large amounts of cedarwood oil  (Allen, 1877; HSDB, 2002).

Animal Data: No 2-year carcinogenicity studies of cedarwood oil or its components in animals were identified in the available literature.

The LD50 values for Virginia cedarwood oil and cedrol are given in Table 3.

Table 3. Acute Toxicity Values for Cedarwood Oil and Cedrol

Compound    Species    Route of administration    LD50  (g/kg)
Virginia cedarwood oil    rat    oral    >5
Virginia cedarwood oil    rabbit    dermal    >5
Cedrol    rabbit    dermal    >5
Source: Sigma-Aldrich (2002a)

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Several limited  studies  reported  a  possible  correlation  between  the  use  of  cedarwood bedding and an increased incidence of spontaneous cancer in animals:

$ American-born C3H-Avy and C3H-AvyfB mice raised in the US have nearly a 100% incidence of liver and mammary tumors.  These strains, bred and reared in Australia on  sawdust  bedding  from  Douglas  fir,  had  almost  no  spontaneous  incidence  of mammary  and  liver  tumors,  particularly  after  the  first  generation.    In  contrast, virtually all C3H-Avy mice reared in Australia but kept on US bedding (cedar) and fed US diets developed mammary tumors.  The authors expressed their opinion that the cedar appeared to be the  “carcinogenic” agent, noting that the results involved a limited number of animals (Sabine et al., 1973).

$ Sabine (1975) conducted follow-up studies to further examine the role of cedar bedding  vs   other   parameters  on  the  spontaneous  incidence  of  tumors  in  the susceptible strains of mice.  Sabine concluded that:

Based on data accumulated over 5 years, the incidences of mammary tumors and  hepatomas in three strains of mice (C3H-Avy, C3H-AvyfB, and CBA/J) housed on  Douglas fir sawdust bedding were significantly lower than the reported figures from US laboratories.

Following submission of his paper, Sabine became aware of a publication by Dr. Heston, of the US National Cancer Institute (NCI).  Heston had provided the Australian  investigators  with their initial colony of C3H-Avy  and C3H- AvyfB mice.    When Heston  bedded two groups of mice on either ¾ pine sawdust and ¼ cedar shavings or pine sawdust, both groups developed very high  incidences  of  spontaneous  mammary  tumors  and  hepatomas.  Heston attributed the lower incidences of spontaneous tumors seen in the Australian study  to  higher  ectoparasite  infestations  and  slightly  lower  growth  rates (Heston, 1975).

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Burkhart and Robinson (1978) described a high rate of rat pup deaths, which the authors felt was probably caused by Eastern cedarwood bedding, either through ingestion of inhalation of toxic compounds in the bedding or through the milk of the dams.

Vlahakis (1977) reported that the first generation of C3H-AvyfB crossbred mice had the same high  incidences of mammary and liver tumors whether they were raised using pine bedding or a mixture of pine plus red cedar shavings.

Short-Term Tests:  No in vitro or in vivo studies evaluating cedarwood oil or its components for mutagenic activity were found in the available literature.

Other Biological Effects:

Hexobarbital Sleeping Time:  Housing the animals using cedarwood bedding resulted in a highly significant reduction of hexobarbital sleeping time in C3H-Avy,  CBA/J, and Swiss Albino mice, indicating induction of the enzymes responsible for hexobarbital oxidation. Using the same methodology, the authors demonstrated enzyme induction in CBA/J mice from Virginia cedarwood oil (Sabine, 1975).

The increase in the duration of hexobarbital hypnosis following exposure of Swiss- Webster mice to cedar shavings was previously reported by Wade and coworkers at the University of Georgia.  These investigators then exposed mice to various fractions of cedarwood for up to 10 days and measured the duration of hexobarbital anesthesia, which suggested that cedrol and cedrene were the  causative agents (Wade et al.,
1968).

Insecticidal Properties: Cedarwood shavings from Juniperus virginiana arrested the life cycle at the 1st  instar stage of the Peanut Trash Bug (Elasmolomus sordidus). It also

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caused the death of colonies of Indian Moths (Plodia interpunctella) and Forage Mites (Tyrophagus putrescentiae). Virginia cedarwood oil (3%), cedrene (2%), and cedrol (2%) were all highly toxic to Peanut Trash Bug colonies. Cedarwood oil and cedrene also affected the  reproductive behavior of adults or hatchability of eggs. Colonies  of  German  cockroaches   (Blatella  germanica)  were  not  affected  by cedarwood from Juniperus virginiana (Sabine, 1975).

Components of cedarwood oils:

$    Cedrene  prevented  the  butylated  hydroxytoluene  (BHT)-induced  inhibition  of lung  tumors  caused  by  intraperitoneal  injection  of  urethan  in  strain  A  mice (Malkinson & Beer, 1984).

$    The effect of cedrene on in vitro hepatic metabolism was studied in Sprague- Dawley  rats.    Administration  of  cedrene  using  the  oral,  intraperitoneal  and inhalation  routes,  increased   the  ethylmorphine  N-demethylase  activity  and cytochrome P-450 content, while it had no effects on aniline hydroxylase activity (Hashimoto et al., 1972).

$    -Thujaplicin, a compound found in the heartwood of the western red cedar (Thuja plicata),  was teratogenic when administered to ICR mice at very high doses.    In vitro, -thujaplicin  induced growth retardation and malformation of cultured embryos harvested at 9 days of gestation. In vivo, 420-1,000 mg/kg of - thujaplicin, given orally to pregnant ICR mice on day 9 of gestation, induced cleft palates and lips, facial dysmorphism, and other malformations at  doses of 560 mg/kg or above in 18-d old fetuses. The oral LD50 for -thujaplicin was 750-800 mg/kg (Ogata et al., 1999).

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•    Ecotoxicological studies on -cedrene showed that the EC50 was 0.044 mg/L at

48 h for Daphnia pulex (Passino-Reader et al., 1997).

Structure Activity Relationships:

Three derivatives of the major chemical constituents of cedarwood oil were selected for review. These chemicals were cedrol methyl ether [CAS No.67874-81-1], acetyl cedrene [CAS No.80449-58-7], and  cedryl acetate [CAS No. 77-54-3]. No information on the carcinogenicity or genotoxicity of these compounds in a search of the National Library of Medicine TOXNET databases, including TOXLINE.  No  information on any of these chemicals was located in the 1999 version of CancerChem, the  CD-ROM version of NCI’s Survey of Compounds Which Have Been Tested for CarcinogenicomActivity (PHS-
149), available from GMA Industries, Inc.

Table 4. Information on Derivatives of the Major Components of Cedarwood Oil.

CH3

17

Prepared for NCI by Technical Resources International, Inc. to support nomination under contract no. N02-CB-07007 (CSWG:05/02; NTP: 9/02)

Cedarwood Oil
8000-27-9

Cedryl acetate
CAS No.: 77-54-3

CH3     CH OCOCH3

CH3
CH3

Fragrance in perfume, fixative, food additive (Allured FFM, 1999; FDA, 2002; Gerhartz,
1988)

18

Prepared for NCI by Technical Resources International, Inc. to support nomination under contract no. N02-CB-07007 (CSWG:05/02; NTP: 9/02)

Cedarwood Oil
8000-27-9

References

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Allured FFM (1999) Cedarwood oil, cedrol, cedrene, cedryl acetate, acetylcedrene. Allured’s
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19

Prepared for NCI by Technical Resources International, Inc. to support nomination under contract no. N02-CB-07007 (CSWG:05/02; NTP: 9/02)

Cedarwood Oil
8000-27-9

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Danish Environmental  Protection  Agency  (2002)  Environmental  and  Health  Assessment  of Substances in  Household Detergents and Cosmetic Detergent Products. [http://www.mst.dk/ udgiv/publications/ 2001/87-7944-596-9/html/kap12_eng.htm]. Searched  May  5, 2002

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20

Prepared for NCI by Technical Resources International, Inc. to support nomination under contract no. N02-CB-07007 (CSWG:05/02; NTP: 9/02)

Cedarwood Oil
8000-27-9

the United Nations. [http://www.fao/org/docrep/V5350e/V5350e00.htm]. Searched May 2, 2002

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Hashimoto, M., Davis, D.C. & Gillette, JR. (1972) Effect of different routes of administration of cedrene on hepatic drug metabolism. Biochem. Pharmacol., 21, 1514-1517

Health Canada (2002) Cedarwood oil.   Drug Product Database. [http://www.hc-sc.gc.ca/hpb/
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opinioa.html]. Searched May 1, 2002

21

Prepared for NCI by Technical Resources International, Inc. to support nomination under contract no. N02-CB-07007 (CSWG:05/02; NTP: 9/02)

Cedarwood Oil
8000-27-9

Laurel Laboratories, Inc. (2002) An Introduction to the Oil of Western Red Cedarwood Pacific.. [http://home.istar.ca/~daijones/index.html]. Searched May 8, 2002

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Malkinson, A.M. & Beer, D.S. (1984) Pharmacologic and genetic studies on the modulatory effects of  butylated hydrxytoluene on mouse lung adenoma formation. J. Natl. Cancer Inst.,
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Oklahoma  State  University  (2001)  Turning  a  problem  into  profit.  [http://www.okstate. edu/ag/impact/impact1.htm]. Searched December 17, 2001

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22

Prepared for NCI by Technical Resources International, Inc. to support nomination under contract no. N02-CB-07007 (CSWG:05/02; NTP: 9/02)

Cedarwood Oil
8000-27-9

Sabine, J.R. (1975) Exposure to an environment containing the aromatic red cedar, Juniperus virginiana: procarcinogenic, enzyme-inducing and insecticidal effects. Toxicology, 5, 221-235

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23

Prepared for NCI by Technical Resources International, Inc. to support nomination under contract no. N02-CB-07007 (CSWG:05/02; NTP: 9/02)