(2E)-3,7-ジメチル-2,6-オクタジエン-1-オン

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

Use foam, dry powder, carbon dioxide.

Fresh air, rest.

Rinse and then wash skin with water and soap.

Rinse with plenty of water (remove contact lenses if easily possible).

Rinse mouth.

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

If material on fire or involved in fire: Use foam, dry chemical, or carbon dioxide. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Keep run-off water out of sewers and water sources.

Environmental considerations- land spill: Dig a pit, pond, lagoon, holding area to contain liquid or solid material. /SRP: If time permits, pits, ponds, lagoons, soak holes, or holding areas should be sealed with an impermeable flexible membrane liner./ Cover solids with a plastic sheet to prevent dissolving in rain or fire fighting water. Dike surface flow using soil, sand bags, foamed polyurethane, or foamed concrete.

Environmental considerations- water spill: Use natural barriers or oil spill control booms to Use natural deep water pockets, excavated lagoons, barriers to trap material at bottom. Remove trapped material with suction hoses.

Environmental considerations- air spill: Apply water spray or mist to knock down vapors.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Remove all ignition sources. Personal protection: chemical protection suit and filter respirator for organic gases and vapours adapted to the airborne concentration of the substance. Do NOT let this chemical enter the environment. Collect leaking liquid in covered containers. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

If material not on fire and not involved in fire: Keep material out of water sources and sewers. Use water spray to knock-down vapors.

Personnel protection: Avoid breathing vapors. Keep upwind. Do not handle broken packages unless wearing appropriate personal protective equipment.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

... The aim of the present study was to analyze the effect of the immunomodulator compounds, Complete Freund Adjuvant (CFA) and cyclosporin A (CsA), administered alone or together with citral on the induction and extent of rat prostatic hyperplasia. Adolescent Wistar rats (42 days old) were given citral alone or combined with CFA or CsA for one month. Semiquantitative analysis of the extent of the hyperplastic lesions was made with the histoscore protocol. CsA did not induce hyperplastic changes or abolish the ability of citral to promote hyperplastic changes or to affect the extent of the lymphocytic exudate in the stroma. CFA itself, however, had a proliferative action on the prostatic epithelium, and it augmented the hyperplastic changes induced by citral and even induced atypical transformations of the acinar epithelium.

The ability of citral to modulate tumor promotion was tested in a two-stage skin carcinogenesis study in hairless mice. The dorsal skins of female skh/hr1 mice were initiated with 0.1 umol dimethylbenzanthracene, and tumors were promoted by twice-weekly application of 10 nmol of tetradecanionyl-phorbol-13-acetate (TPA) for 20 weeks. Prior to each TPA application, citral was given with 0, 1 or 10 umol. Citral had a dose-dependent inhibitory effect on tumor production in the TPA promoted groups.

Citral inhibits the formation of retinoic acid from retinol in mouse epidermis. Since skin-carcinogenesis is sensitive to retinoid status, and retinoic acid may be the active form of vitamin A in the epidermis, citral was tested for its ability to modulate tumor promotion in a two-stage skin-carcinogenesis study in hairless mice. The dorsal skins of female SKH/HRL mice were initiated with 0.1 umol dimethylbenzanthracene, and tumors were promoted by twice-weekly application of l0 nmol of tetradecanoylphorbol-13-acetate (TPA) for 20 weeks. Prior to each TPA application groups were dosed with 0, l umol or 10 umol citral. Citral had a dose-dependent inhibitory effect on tumor-production in the TPA promoted groups. At 10 weeks of promotion the percentage of mice with tumors were 88%, 72% and 60%, for the 0, 1 and l0 umol citral treated groups, and the numbers (mean + or- SD) of tumors per affected animal were 7.3 + or - 6.6, 3.9 + or - 4.2, and 3.7 + or - 3.5, respectively. At 15 weeks of promotion the tumor incidence was 96%, 96% and 84%, respectively, and the number of tumors per affected animal were 9.5 + or - 6.8, 7.2 + or - 4.6 and 4.5 + or - 3.3, respectively. The mice in the high dose citral group had significantly fewer tumors. When the study was terminated at 20 weeks of promotion all mice had at least one tumor, but the number of tumors per affected mouse were lower in the citral treated groups.

LC50 Oryzias latipes (Medaka) 6.1 mg/L/24 hr; semi-static, 21-23 °C, pH 6.9-7.3, dissolved oxygen 4.9-9.1 mg/L /98.9% pure/

LC50 Oryzias latipes (Medaka) 5.8 mg/L/48 hr; semi-static, 21-23 °C, pH 6.9-7.3, dissolved oxygen 4.9-9.1 mg/L /98.9% pure/

LC50 Oryzia latipes (Medaka) 4.1 mg/L 96 hr; semistatic bioassay

LC50 Leuciscus idus 4.6-10 mg/L 96 hr; static bioassay

For more Ecotoxicity Values (Complete) data for CITRAL (8 total), please visit the HSDB record page.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 83(SRC), determined from a water solubility of 1,340 mg/L(2) and a regression-derived equation(3), indicates that citral is expected to have high mobility in soil(SRC). Volatilization of citral from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.3X10-5 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Citral is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.1X10-2 mm Hg(SRC), determined from a fragment constant method(5). A theoretical BOD of 92% using activated sludge and the Japanese MITI test(6) suggests that biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 83(SRC), determined from a water solubility of 1,340 mg/L(2) and a regression-derived equation(3), indicates that citral is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 4.3X10-5 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 28 hrs and 12 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 10(SRC), from its water solubility(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A theoretical BOD of 92% using activated sludge and the Japanese MITI test(6) suggests that biodegradation may be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), citral, which has an estimated vapor pressure of 9.1X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase citral is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3 hrs(SRC), calculated from its rate constant of 1.4X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Citral does contain chromophores that absorb at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight(4).

Citral was rapidly absorbed from the gastro -intestinal tract. Much of an applied dermal dose was lost due to its extreme volatility, but the citral remaining on the skin was fairly well absorbed. Citral was rapidly metabolized and excreted as metabolites. Urine was the major route of elimination. Acute toxicity of this chemical is low in rodents because the oral or dermal LD50 values were more than 1000 mg/kg. This chemical is irritating to skin and not irritating to eyes in rabbits. There is some evidence that this chemical is a human skin sensitizer. Several repeated dose oral studies show no adverse effect of citral at less than 1,000 mg/kg/day exposure and some histological changes in the nasal cavity or forestomach, the first exposure sites, probably due to irritation, at more than 1,000 mg/kg/day. Male and female F344/N rats received microencapsulated citral in feed at concentrations of 0, 0.63, 1.25, 2.5, 5 and 10% (resultant doses: 0, 142, 285, 570, 1,140 and 2,280 mg/kg/day) for 14 days. Minimal to mild hyperplasia and/or squamous metaplasia of the respiratory epithelium was observed in nasal cavity without inflammatory response at 1,140 and 2,280 mg/kg/day of both sexes. The NOAEL was established at 570 mg/kg/day. In an OECD preliminary reproduction toxicity screening test [TG 421], citral was administered to Crj:CD (SD) rats by gavage at doses of 0, 40, 200 and 1,000 mg/kg/day in males for 46 days and in females for 39- 50 days including before and through mating and gestation periods and until day 3 of lactation. Squamous hyperplasia, ulcer and granulation in lamina propria were observed in the forestomach at 1,000 mg/kg/day of both sexes. Therefore, the NOAEL for repeated dose toxicity was 200 mg/kg/day for both sexes. As for reproductive toxicity in the above preliminary reproductive study, no effects were detected in reproductive ability, organ weights or histopathology of the reproductive organs of both sexes, and delivery or maternal behavior. However, body weights of male and female pups were reduced in the 1000 mg/kg group. Therefore, an oral NOAEL for developmental toxicity was 200 mg/kg/day. In a teratogenicity study, SD pregnant rats were exposed to citral by inhalation for 6 hr/day on gestation days 6-15 at mean concentration of 0, 10 or 34 ppm as vapour, or 68 ppm as an aerosol/vapour mixture. Even in the presence of the maternal effects, no significant teratogenicity was noted at 68 ppm. An inhalation NOAEL of teratogenicity was established at 68 ppm (423 mg/m3). Seven bacterial reverse mutation studies indicate negative results with and without metabolic activation. As for non-bacterial in vitro study, two chromosomal aberration results in Chinese hamster cells are negative however one positive result in sister chromatid exchange is given in the same cells. Add itionally, two in vivo micronucleus tests in rodents indicate negative results. Based on the above information, the genotoxic potential of citral can be considered to be negative. A NTP study shows that there was no evidence of carcinogenic activity in male/female rats and male mice but some evidence of malignant lymphoma in female mice (up to 4,000 ppm in feed in rats and up to 2,000 ppm in feed in mice). Dermal application of citral induces prostate hyperplasia with low severity only in some strains of rats. However, the NTP oral carcinogenicity studies in rats and mice found no evidence of lesions (neoplastic or non-neoplastic) in any male reproductive organ, including the prostate. The health significance of the effects seen in the dermal studies in rats is uncertain due to dramatic strain differences and it is noted that the work has primarily been performed in a single laboratory.

Originally reported to be found in lemongrass oil (Cymbopogan flexuosus (Ness.) Stapf.) in amounts up to 75%, citral has also been identified in Litsea citrata (approx 90%), L. cubeba Blume. (approx 70%), Lindera citriodora (approx 65%), Backhousia citriodora (approx 85-97%), Calypranthes porricultata (approx 62%), Leptspermum liversidgei var. A. leaves (approx 70-80%), Ocimum gratissimum (approx 66.5%) and Citrus aurantifolia leaves (petitgrain, approx 36%)(1). Citral was detected (<1% of total area of identified peaks) in the leaves of Eucalyptus dunnii but not detected in E. saligna nor E. citriodora(2).

Cough.

Redness.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=5392-40-5]

The Koc of citral is estimated as 83(SRC), using a water solubility of 1,340 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that citral is expected to have high mobility in soil.

3,7-Dimethyl-2,6-octadienal (CAS # 5392-40-5) was evaluated for dermal sensitization. The test substance was applied at a dosage of 0.5 ml to the occluded upper arms of 42 human subjects. The final challenge application applied two patches, one to the original site and one to a site not previously sensitized. No evidence of primary irritation or sensitization was observed.

3,7-Dimethyl-2,6-Octadienal (CAS # 5392-40-5) was evaluated for primary dermal irritation. The test substance was applied (undiluted) at a dosage level of 0.5 ml to 6 New Zealand albino rabbits for 24 hours. Clinical signs included moderate erythema and edema, and loosening of the scab edges in 14-17 days, showing injury in depth. The test substance was determined to be corrosive.

A case report for 3,7-Dimethyl-2,6-Octadienal (CAS # 5392-40-5) was submitted because of an adverse health effect from an Exxon employee who complained of "congestion, nausea, headaches, sore throat, eyes burning, tightness in chest", during the run of lemon scent bags containing the product "lemon scent resin concentrate". The product contains one material, Citral, which is know to have sensitizing potential. Citral is a skin irritant and may be capable of eliciting skin allergies (delayed contact hypersensitivity). Further claims of adverse health effects were alleged from a clerical employee in the Clinton, Massachusetts plant who suffered a "distinct allergic reaction" to the scent of a raw material used in the manufacture of the subject chemical. The employee saw a physician at the time of the incident, who "administered a shot which reduced the swelling, and after a few minutes returned her breathing to normal". The allergic response is similar to "anaphylactic shock".

3,7-Dimethyl-2,6-Octadienal (CAS # 5392-40-5) was evaluated for genotoxicity. Tests for cytogenetic effects were performed in chinese hamster ovary cells. The test substance was negative for induction of chromosome aberrations (CA) and positive for induction of sister chromatid exchanges (SCE). No further information was submitted.

Synthetic flavoring substances and adjuvants /for human comsumption/ that are generally recognized as safe for their intended use, within the meaning of section 409 of the Act. Citral is included on this list.

Synthetic flavoring substances and adjuvants /for animal drugs, feeds, and related products/ that are generally recognized as safe for their intended use, within the meaning of section 409 of the Act. Citral is included on this list.

Component of many commercial oils including lemon grass, verbena, lemon, and orange; [Merck Index] Used as a flavoring agent and fragrance and an intermediate for the synthesis of other fragrances, vitamin A, ionone, and methylinone; [HSDB]

Reported uses (FEMA, 1994): Alcoholic and nonalcoholic beverages, baked goods, cheese, chewing gum, condiment (relish), frozen dairy, gelatin (pudding), gravies, hard and soft candy, meat products.

Used primarily as a starting material for the manufacturing of fragrance ingredients. Also used as a fragrance ingredient in fragrance compositions typically at a level of 0.1 to 1%. These compositions are used to perfume a wide variety of consumer products.

Intermediate for other fragrances

In the synthesis of vitamin A, ionone and methylinone. As a flavor and in perfumery for its citrus effect.

(1972) 7.59X10+6 G

(1975) 5.90X10+7 G

2023: 8,500,000 - <10,000,000 lb

2023: 50,000 - <250,000 lb

(1972) 1.32X10+7 G (SALES OF CITRAL A)

(1973) 3.95X10+7 G (SALES OF CITRAL A)

Production volumes for non-confidential chemicals reported under the Inventory Update Rule. [Table#2662]

This chemical is listed as a High Production Volume (HPV) (65FR81686). Chemicals listed as HPV were produced in or imported into the U.S. in >1 million pounds in 1990 and/or 1994. The HPV list is based on the 1990 Inventory Update Rule. (IUR) (40 CFR part 710 subpart B; 51FR21438).

Consumption (U.S.): Annual: 59,500.00 lb. (From the PAFA database, originating from the NAS survey of 1987 and assumes only 60% of poundage was reported.) Individual: 0.05042 mg/kg/day

Europe: Most recent annual volume (kg): 47,997. Intake (eaters only) (ug/day) 6849.

Use in fragrances in the USA amounts to less than 75,000 lbs/yr

Concentration in final product (%). [Table#2661]

Fragrance

Fragrance

Flavoring and nutrient

Fragrance

Citral

3,7-Dimethyl-2,6-octadienal; Geranial (trans-citral); Neral; Geranial; Lemarome (commercial name)

IFRA_STD_021.pdf

49

IFRA 51st Amendment - Guidance for the use of IFRA Standards

Restriction: This material should be used only in the limited quantity as stated in the Standard

DEHYDROGENATION OF A GERANIAL-NERAL MIXTURE OBTAINED FROM BETA-PINENE

SYNTHESIS FROM ISOPRENE.

Principal constituent of lemongrass oil & can be isolated by fractional distillation. Obtained synthetically by oxidation of geraniol, nerol, or linalool by chromic acid.

Citral is isolated by distillation from lemongrass oil ... and from Litsea cubeba oil ... It is the main component of these oils.

For more Methods of Manufacturing (Complete) data for CITRAL (8 total), please visit the HSDB record page.

Citral has a strong, lemon-like, odor and a characteristic bittersweet taste. Commercially, the product is a mixture of two geometric isomers - alpha-citral and beta-citral, each exhibiting cis- and trans-isomers because of the position of the double bond. Geranial (trans-) and neral (cis-).

Citral from natural sources is a 2:1 mixture of two geometric isomers geranial and neral

Commercial material is a mixture of alpha and beta isomers.

Grade: Technical; pure; FCC

Cosmetics product ingredient: Citral (3,7-Dimethyl-2,6-octadienal; (E)-3,7-dimethylocta-2,6-dienal; (Z)-3,7-dimethylocta-2,6-dienal; Geranial; Neral)

Information on 2 consumer products that contain Geranial in the following categories is provided:

Information on 403 consumer products that contain Citral in the following categories is provided:

Fragrance Ingredients

Fragrance Ingredients

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavoring Agents -> JECFA Flavorings Index

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Flavouring Agent -> FLAVOURING_AGENT -> JECFA Functional Classes

Other (requires additional information)

Soap, Cleaning Compound, and Toilet Preparation Manufacturing

2,6-Octadienal, 3,7-dimethyl-, (2E)-: ACTIVE

2,6-Octadienal, 3,7-dimethyl-: ACTIVE

WILL CAUSE DISCOLORATION OF WHITE SOAPS & ALKALINE COSMETICS.

In public use before the 1900s.