Citral

152.23

152.23

1721871

226-394-6

758ZMW724E

1725

6170

2810

DTXSID6024836

Mobile pale yellow liquid

2912190090

17.1

3

colorless to light yellow Liquid

0.891-0.897 g/cm³ @ Temp: 15 °C

<-10 °C

227 °C

215 °F

1.457

Practically insoluble in water

2-8°C

0.2 mm Hg ( 200 °C)

5 (vs air)

LD50 orally in rats: 4.96 g/kg (Opdyke)

4.3-9.9%(V)

Strong lemon odor

Taste threshold values: Detection: 28 to 120 ppb; alpha-citral, 32 to 460 ppb; beta-citral, 30 to 460 ppb.

ACID VALUE: 5.0 MAX

Henry's Law constant = 4.35X10-5 atm-cu m/mol at 25 °C (est)

VAPOR PRESSURE: 5 MM HG @ 91-95 °C /GERANIAL/|Light oily liquid with a lemon odor not as intense but sweeter than geranial; BP: 91-92 °C at 2.6 mm Hg; density: 0.8869 at 20 °C/4 °C; Index of refraction: 1.48690 at 20 °C/D miscible with ether, benzyl benzoate, propylene glycol, diethyl phthalate, glycerol, mineral oils, alc, essential oils; practically insol in water /Neral/|Light oily liquid with strong lemon odor. BP: 92-93 °C at 2.6 mm Hg; Index of refraction: 1.4892 at 20 °C/D; density: 0.8888 at 20 °C/4 °C; miscible with ether, benzyl benzoate, propylene glycol, diethyl phthalate, glycerol, mineral oils, alc, essential oils; practically insol in water /Geranial/|Hydroxyl radical reaction rate constant = 1.36X10-10 cu cm/molec-sec at 25 °C (est)

Insoluble in water.

Aldehydes

CITRAL is an aldehyde. Aldehydes are frequently involved in self-condensation or polymerization reactions. These reactions are exothermic; they are often catalyzed by acid. Aldehydes are readily oxidized to give carboxylic acids. Flammable and/or toxic gases are generated by the combination of aldehydes with azo, diazo compounds, dithiocarbamates, nitrides, and strong reducing agents. Aldehydes can react with air to give first peroxo acids, and ultimately carboxylic acids. These autoxidation reactions are activated by light, catalyzed by salts of transition metals, and are autocatalytic (catalyzed by the products of the reaction). The addition of stabilizers (antioxidants) to shipments of aldehydes retards autoxidation. This compound can react with alkalis and strong acids. It can readily isomerize. (NTP, 1992)

225 °C

III

8

1760

1

38-43

24/25-37

RG5075000

Xi

Cool. Ventilation along the floor. Provision to contain effluent from fire extinguishing. Store in an area without drain or sewer access.

Stable. but readily isomerizes. Incompatible with alkalies, strong oxidizing agents, strong acids. Combustible. Air and light sensitive.

P280-P305 + P351 + P338

H315-H317-H319

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.

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.

European Chemicals Bureau; IUCLID Dataset, Citral (CAS No. 5392-40-5). Available from the database query page: http://ecb.jrc.it/esis/esis.php as of January 22, 2007.|FAO/WHO Joint Expert Committee on Food Additives; WHO Food Additives Series 52: Aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids, and related esters (2004). Available from Database Query page at: http://www.inchem.org/pages/jecfa.html as of February 21, 2007.|DHHS/NTP; Toxicology and Carcinogenesis Studies of Citral (Microencapsulated) (CAS No. 5392-40-5) in F344/N Rats and B6C3F1 Mice (Feed Studies) (January 2003) Technical Rpt Series No. 505 NIH Pub No. 03-4439. Available from the Database Query page at: http://ntp-server.niehs.nih.gov/ as of February 21, 2007.

This chemical is combustible. (NTP, 1992)|Combustible. Above 82 °C explosive vapour/air mixtures may be formed.

|Warning|H315: Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P272, P280, P302+P352, P321, P332+P313, P333+P313, P362, P363, and P501|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P272, P280, P302+P352, P305+P351+P338, P321, P332+P313, P333+P313, P337+P313, P362, P363, and P501|Aggregated GHS information provided by 321 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H315 (99.97%): Causes skin irritation [Warning Skin corrosion/irritation]|Aggregated GHS information provided by 3062 companies from 17 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Danger|H225 (71.38%): Highly Flammable liquid and vapor [Danger Flammable liquids]|P210, P233, P240, P241, P242, P243, P261, P264, P272, P273, P280, P302+P352, P303+P361+P353, P305+P351+P338, P321, P332+P313, P333+P313, P337+P313, P362, P363, P370+P378, P403+P235, and P501|Aggregated GHS information provided by 311 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H227: Combustible liquid [Warning Flammable liquids]|P201, P202, P210, P261, P264, P272, P280, P281, P302+P352, P308+P313, P321, P332+P313, P333+P313, P362, P363, P370+P378, P403+P235, P405, and P501

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: ELIMINATE all ignition sources (no smoking, flares, sparks or flames in immediate area). Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. (ERG, 2016)

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. (ERG, 2016)|Irritating to skin and may cause sensitization by skin contact. Avoid contact with skin and eyes. Wear suitable gloves.|Personnel protection: ... Wear positive pressure self-contained breathing apparatus.

Combustible

It is rather endothermic.|Explosive limits , vol% in air: 4.3 - 9.9

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.

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.

Irritant effect of 19 oils & 20 synthetic perfumes used in cosmetics were tested on skin of 50 male volunteers. Citral @ 32% concn was the most irritating of perfumes in human patch test.|Irritating to skin.|A cumulative irritation study was carried out on 8 volunteers. Patches were placed on the back daily, removed at 24 hr and read and them replaced with a fresh patch, over a period of 21 days. /Citral concentrations tested included 1, 4 and 8% in petrolatum./ The 8 % concentration was found to be a marginal irritant.|During an investigation of an outbreak of dermatitis following the introduction of a lemon-scented detergent, citral was shown by patch tests to be a strong primary irritant if applied in association with heat; 10% citral induced slight responses at 23 °C and pronounced responses at 43 °C.

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.

Cool. Ventilation along the floor. Provision to contain effluent from fire extinguishing. Store in an area without drain or sewer access.

No indication can be given about the rate at which a harmful concentration of this substance in the air is reached on evaporation at 20 °C.

The substance is irritating to the skin.

Repeated or prolonged contact may cause skin sensitization.

NO open flames. Above 82 °C use a closed system and ventilation.

PREVENT GENERATION OF MISTS!

Use ventilation, local exhaust or breathing protection.

Protective gloves. Protective clothing.

Wear safety spectacles.

| 2 - Materials that, under emergency conditions, can cause temporary incapacitation or residual injury.| 1 - Materials that must be preheated before ignition can occur. Materials require considerable preheating, under all ambient temperature conditions, before ignition and combustion can occur.| 0 - Materials that in themselves are normally stable, even under fire conditions.

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.

... 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.

LD50 Mouse oral 1440 mg/kg bw|LD50 Mouse oral 3297 mg/kg bw|LD50 Mouse male oral 2007 mg/kg bw (synthetic citral)|LD50 Rat oral 4950 mg/kg bw|For more Non-Human Toxicity Values (Complete) data for CITRAL (12 total), please visit the HSDB record page.

14-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were fed diets containing starch microcapsules with a load of 31.3% citral. The concentration of citral in the diet was 3,900, 7,800, 15,600, or 31,300 ppm microencapsulated citral (equivalent to average daily doses of approximately 345, 820, 1,785, and 1,585 mg citral/kg body weight to males and 335, 675, 1,330, and 2,125 mg/kg to females) for 14 weeks. Additional groups of 10 male and 10 female rats received untreated feed (untreated controls) or feed containing placebo microcapsules (vehicle controls). In the second week of the study, all rats in the 31,300 ppm groups were killed moribund. Mean body weights of exposed males and females that survived to the end of the study were generally significantly less than those of the vehicle controls. Feed consumption by 15,600 and 31,300 ppm males and females was less than that by the vehicle controls during the first week of the study. Males and females in the 31,300 ppm groups exhibited listlessness, hunched posture, absent or slow paw reflex, and dull eyes. Exposure of rats to citral may have been associated with forestomach epithelial hyperplasia and hyperkeratosis, bone marrow atrophy and hemorrhage, and nephrotoxicity. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were fed diets containing 3,900, 7,800, 15,600, or 31,300 ppm microencapsulated citral (equivalent to average daily doses of approximately 745, 1,840, 3,915, and 8,110 mg/kg to males and 790, 1,820, 3,870, and 7,550 mg/kg to females) for 14 weeks. Additional groups of 10 male and 10 female mice received untreated feed (untreated controls) or feed containing placebo microcapsules (vehicle controls). In the second week of the study, four males in the 31,300 ppm group were killed moribund. Mean body weights of all exposed groups of males and females were significantly less than those of the vehicle controls. Feed consumption by females exposed to 7,800 ppm or greater was less than that by the vehicle controls during the first week of the study. By the end of the study, feed consumption by all exposed groups was greater than that by the vehicle controls. Mice in the 15,600 and 31,300 ppm groups were generally thin and lethargic; a few males in the 7,800 ppm group were also thin. The incidences of ovarian atrophy were significantly increased in females exposed to 15,600 or 31,300 ppm.|2-YEAR STUDY IN RATS Groups of 50 male and 50 female F344/N rats were fed diets containing 1,000, 2,000, or 4,000 ppm microencapsulated citral for 2 years. Additional groups of 50 male and 50 female rats received untreated feed (untreated controls) or feed containing placebo microcapsules (vehicle controls). Dietary concentrations of 1,000, 2,000, and 4,000 ppm delivered average daily doses of approximately 50, 100, and 210 mg/kg to males and females. Survival of all exposed groups of males was significantly greater than that of the vehicle control group. Mean body weights of rats exposed to 4,000 ppm were generally less than those of the vehicle controls from week 49 (males) or 25 (females) to the end of the study. Feed consumption by exposed groups was similar to that by the vehicle controls. No neoplasms or nonneoplastic lesions were attributed to exposure to citral. 2-YEAR STUDY IN MICE Groups of 50 male and 50 female B6C3F1 mice were fed diets containing 500, 1,000, or 2,000 ppm microencapsulated citral for 2 years. Additional groups of 50 male and 50 female mice received untreated feed (untreated controls) or feed containing placebo microcapsules (vehicle controls). Dietary concentrations of 500, 1,000, and 2,000 ppm delivered average daily doses of approximately 60, 120, and 260 mg/kg to males and females. Survival of exposed males and females was similar to that of the vehicle control groups. Mean body weights of mice exposed to 1,000 or 2,000 ppm were generally less than those of the vehicle controls throughout the study, and mean body weights of 500 ppm females were less from week 30 to the end of the study. Feed consumption by the exposed groups was similar to that by the vehicle controls. The incidences of malignant lymphoma occurred with a positive trend in female mice, and the incidence in 2,000 ppm females was significantly greater than that in the vehicle control group. Tissues most commonly affected by malignant lymphoma were the spleen, mesenteric lymph node, thymus, and, to a lesser extent, the ovary. Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of citral in male or female F344/N rats exposed to 1,000, 2,000, or 4,000 ppm. There was no evidence of carcinogenic activity of citral in male B6C3F1 mice exposed to 500, 1,000, or 2,000 ppm. There was equivocal evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of malignant lymphoma.|Citral was not mutagenic in S. typhimurium strain TA98, TA100, TA1535, or TA1537 with or without induced rat or hamster liver S9 enzymes. In cytogenetic tests with cultured Chinese hamster ovary cells, citral induced sister chromatid exchanges with and without S9, but chromosomal aberrations were not significantly increased after exposure to citral, with or without S9. Negative results were obtained in an in vivo bone marrow micronucleus test in male B6C3F1 mice treated by intraperitoneal injection with 250 to 750 mg/kg daily for 3 days. Likewise, no increases in the frequencies of micronucleated erythrocytes were observed in peripheral blood samples collected from male and female mice within 24 hours of the final exposure in the 14-week study. In conclusion, citral gave negative results in in vitro and in vivo tests for genotoxicity, with the exception of the in vitro mammalian cell test for sister chromatid exchange induction.

Citral is a constituent of many commercial oils such as lemon grass, verbena, lemon, and orange(1,2).|Citral from natural sources is a 2:1 mixture of two geometric isomers geranial and neral|...FOUND IN: LITSEA CITRATA (APPROX 90%), LITSEA CUBEBA BLUME (APPROX 70%), LINDERA CITRIODORA (APPROX 65%), BACKHOUSIA CITRIODORA (APPROX 95-97%), CALYPRANTHES PARRICULATA (APPROX 62%), LEPTOSPERMUM LIVERSIDGEIVAR A LEAVES (APPROX 70-80%), & OCIMUM GRATISSIUMUM (APPROX 66.5%). ALSO PRESENT IN LEMON (2-5%), LIME (6-9%), & CITRUS AURANTIFOLIA LEAVES (PETITGRAIN, APPROX 36%).

Citral's production and use in perfumery, as a flavor, and in chemical synthesis(1) may result in its release to the environment through various waste streams(SRC).

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).

The rate constant for the vapor-phase reaction of citral with photochemically-produced hydroxyl radicals has been estimated as 1.4X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of citral with ozone has been estimated as 4.4X10-16 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 37 minutes at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). Reaction with nitrate radicals may be important(3). Citral is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(4). Citral does contain chromophores that absorb at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight(4).

An estimated BCF of 10 was calculated in fish for citral(SRC), using a water solubility of 1,340 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

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.

The Henry's Law constant for citral is estimated as 4.35X10-5 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that citral is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 28 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 12 days(SRC). Citral's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). 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(3).

Citral is present in lemon (2-5%) and lime (6-9%)(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 200,484 workers (83,180 of these are female) are potentially exposed to citral in the US(1). Occupational exposure to citral may occur through inhalation and dermal contact with this compound at workplaces where citral is produced or used(SRC). Monitoring and use data indicate that the general population may be exposed to citral via inhalation, ingestion of food, and dermal contact with this compound and other consumer products containing citral(SRC).

Male Fischer F344 rats were given citral labelled with 14C at the C1 and C2 positions in a single oral dose of 5, 50, or 500 mg/kg bw or an intravenous dose of 5 mg/kg bw. After 72 h, the animals were sacrificed and tissues and excreta analyzed for radioactivity. Most radiolabel was excreted in the urine, feces, and expired air as 14CO2 or [14C]citral within 24 hr, regardless of the dose or route of administration. At the lowest oral dose, 83% of the radiolabel was recovered within 72 hr (51% in urine, 12% in feces, 17% as expired 14CO2, <1% as expired [14C]citral, and 3% in total tissues). Production of 14CO2 essentially ceased 12 hr after treatment, and the amount of 14C found in any tissue was very small (<2%). This excretion profile did not change much with increasing oral dose, although ... oxidation to CO2 was somewhat greater at the lowest dose.|In rat & mouse orally admin citral was rapidly absorbed from gi tract, resulting in uniform distribution of label throughout body of mouse by 12 hr. Radioactivity was excreted rapidly, major route being urinary tract. No evidence for long-term storage in body.|The disposition of citral was studied in male Fischer rats after iv, po, and dermal treatments. The pattern of distribution and elimination was the same after iv or oral exposure. Urine was the major route of elimination of citral-derived radioactivity, followed by feces, (14)C02, and expired. However, after dermal exposure, relatively less of the material was eliminated in the urine and more in the feces, suggesting a role for first-pass metabolism through the skin. Citral was almost completely absorbed orally; due to its extreme volatility, much of an applied dermal dose was lost. The citral remaining on the skin was fairly well absorbed. No effect of oral dose, from 5 to 500 mg/kg, was detected on disposition. Although the feces was a minor route of excretion, approximately 25% of the administered dose was eliminated via the bile within 4 hr of an iv dose. The metabolism of citral was both rapid and extensive. Within 5 min of an iv dose, no unmetabolized citral could be detected in the blood. Repeated exposure to citral resulted in an increase in biliary elimination, without any significant change in the pattern of urinary, fecal, or exhaled excretion. This suggests that citral may induce at least one pathway of its own metabolism. The rapid metabolism and excretion of this compound suggest that significant bioaccumulation of citral would not occur.

Citral ... in experimental animals ... is converted in part to the so-called Hildebrandt acid in which a double omega oxidation has taken place.|Citral is a naturally occurring aliphatic aldehyde of the terpene series and is an isomeric mixture of geranial and neral. In this study, urinary metabolites of citral in male F344 rats were characterized. Stereospecific oxidation of citral at the C-8 methyl was investigated, as was the hydrolytic sensitivity of biliary and urinary metabolites. For metabolite identification, urine was collected over dry ice for 24 hr after a single po 500 mg/kg dose of (l4)C citral. Elimination in urine was rapid, with approximately 50% of the dose excreted within 24 hr. Citral was rapidly metabolized and excreted as metabolites, including several acids and a biliary glucuronide. Seven urinary metabolites were isolated and identified: 3-hydroxy-3,7-dimethyl-6-octenedioic acid; 3,8-dihydroxy-3,7-dimethyl-6-octenolc acid; 3,9-dihydroxy-3,7-dimethyl-6-octenolc acid; E- and Z-3,7-dimethyl-2,6-octadienedioic acid; 3,7-dimethyl-6-octenedioic acid; and E-3,7-dimethyl-2,6-octadienoic acid. Although citral is an alpha,beta-unsaturated aldehyde and has the potential of being reactive, the urinary metabolites of citral appear to arise from metabolic pathways other than nucleophilic addition to the double bond.|Reports of the in vivo metabolism of citral suggest that a primary route of metabolism is conversion to the corresponding acid presumably by aldehyde dehydrogenases. In the present study, hepatic mitochondrial and cytosolic fractions were prepared from male Sprague-Dawley rats to assess in vitro metabolism of citral. Evidence of aldehyde dehydrogenases-mediated citral oxidation was not seen in either subcellular fraction. On the contrary, citral was found to be a potent inhibitor of acetaldehyde oxidation by the low-KM mitochondrial form of aldehyde dehydrogenases. Measurement of the in vitro acetaldehyde oxidation rates of this isozyme in the presence of citral lead to the estimation of a Ki of 360 nM. It was observed that citral was readily reduced to the corresponding alcohol by alcohol dehydrogenase in the cytosolic fraction. The reduction of citral in the presence of NADH proceeded at two distinct rates. It is possible that the differential alcohol dehydrogenase-mediated reduction rates of citral are the result of varying affinities for the enzyme of two citral, isomers, geranial (trans) and neral (cis).

Low concentrations of citral (3,7-dimethyl-2,6-octadienal), ... inhibited E1, E2 and E3 isozymes of human aldehyde dehydrogenase (EC1.2.1.3). The inhibition was reversible on dilution and upon long incubation in the presence of NAD+; it occurred with simultaneous formation of NADH and of geranic acid. Thus, citral is an inhibitor and also a substrate. Km values for citral were 4 microM for E1, 1 microM for E2 and 0.1 microM for E3; Vmax values were highest for E1 (73 nmol/min/mg), intermediate for E2 (17 nmol/min/mg) and lowest (0.07 nmol/min/mg) for the E3 isozyme. Citral is a 1 : 2 mixture of isomers: cis isomer neral and trans isomer, geranial; the latter structurally resembles physiologically important retinoids. Both were utilized by all three isozymes; a preference for the trans isomer, geranial, was observed by HPLC and by enzyme kinetics. With the E1 isozyme, both geranial and neral, and with the E2 isozyme, only neral obeyed Michaelis-Menten kinetics. With the E2 isozyme and geranial sigmoidal saturation curves were observed with S0.5 of approximately 50 nM; the n-values of 2-2.5 indicated positive cooperativity. Geranial was a better substrate and a better inhibitor than neral. The low Vmax, which appeared to be controlled by either the slow formation, or decomposition via the hydride transfer, of the thiohemiacetal reaction intermediate, makes citral an excellent inhibitor whose selectivity is enhanced by low Km values. The Vmax for citral with the E1 isozyme was higher than those of the E2 and E3 isozymes which explains its fast recovery following inhibition by citral and suggests that E1 may be the enzyme involved in vivo citral metabolism.|Essential oil constituents were tested for their neurophysiological effects in Periplaneta americana and Blaberus discoidalis /cockroaches/ ... Geraniol and citral had similar depressive effects but increased spontaneous firing at lower doses (threshold 2.5 x 10-4 M). Similar effects occurred in dorsal unpaired median (DUM) neurons, recorded intracellularly in the isolated terminal abdominal ganglion of P. Americana. ... citral produced biphasic effects (excitation at 10-4 M, depression at 2 x 10-3 M). All oils decreased excitability of silent DUM neurons that were depolarised by applied current... All oils reduced spike undershoot. Low doses of citral and geraniol (threshold ca. 10-4 M) reversibly increased the frequency of spontaneous foregut contractions and abolished them at 2 x 10-3 M (together with response to electrical stimulation).

SYMPTOMS: Symptoms of exposure to this compound may include contact dermatitis. ACUTE/CHRONIC HAZARDS: This compound is a local irritant. When heated to decomposition it emits acrid smoke and fumes. (NTP, 1992)

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. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Fresh air, rest.

Rinse and then wash skin with water and soap.

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

/HUMAN EXPOSURE STUDIES/ IRRITANT EFFECT OF 19 OILS & 20 SYNTHETIC PERFUMES USED IN COSMETICS WERE TESTED ON SKIN OF 50 MALE VOLUNTEERS. CITRAL @ 32% CONCN WAS THE MOST IRRITATING OF PERFUMES IN HUMAN PATCH TEST.[MOTOYOSHI K ET AL; COSMET TOILET 94 (AUG): 41 (1979)]|/HUMAN EXPOSURE STUDIES/ In a cumulative irritation study, the 8 % concentration was found to be marginal irritant after 21- days exposure ... On the other hand, numerous samples of citral tested at 1 to 8 % produced no irritation after 48-hr closed patch tests on twelve different panels of human subjects.|/HUMAN EXPOSURE STUDIES/ A cumulative irritation study was carried out on 8 volunteers. Patches were placed on the back daily, removed at 24 hr and read and then replaced with a fresh patch, over a period of 21 days. /Citral concentrations tested included 1, 4 and 8% in petrolatum./ The 8 % concentration was found to be a marginal irritant.|/SIGNS AND SYMPTOMS/ During an investigation of an outbreak of dermatitis following the introduction of a lemon-scented detergent, citral was shown by patch tests to be a strong primary irritant if applied in association with heat; 10% citral induced slight responses at 23 °C and pronounced responses at 43 °C.[ROTHENBORG HW ET AL; CONTACT DERMATITIS 3 (1): 37 (1977)]|For more Human Toxicity Excerpts (Complete) data for CITRAL (7 total), please visit the HSDB record page.

(E)-citral

Cough.

Redness.

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#2663]

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

All other chemical product and preparation manufacturing|2,6-Octadienal, 3,7-dimethyl-: ACTIVE|2,6-Octadienal, 3,7-dimethyl-, (2E)-: ACTIVE|2,6-Octadienal, 3,7-dimethyl-, reaction products with Et alc.: ACTIVE|WILL CAUSE DISCOLORATION OF WHITE SOAPS & ALKALINE COSMETICS.|In public use before the 1900s.|Citral, trans-cinnamaldehyde, (-)-perillaldehyde, (-)-citronellal, eugenol and carvacrol were tested for their influence on microbial count in air by vaporizing with an air washer. The highest antibacterial activity was observed when (-)-perillaldehyde was sprayed. The average reduce of germ count was 53%. On the other hand, the antimicrobial activity of eugenol was the lowest of these six compounds. The average reduction of germ count was 13%. When water without volatile compounds was sprayed, the colony forming units increased. These results suggest the utility of selected aroma-compounds for the control of bacteria in the room.|NON-ALCOHOLIC BEVERAGES 9.2 PPM; ICE CREAM, ICES, ETC 23 PPM; CANDY 41 PPM; BAKED GOODS 43 PPM; CHEWING GUM 170 PPM.

HSLC PROCEDURE WAS FASTER & MORE CONVENIENT THAN GLC FOR CITRAL DETERMINATION.|ON ACIDIFICATION WITH METHANOLIC H2SO4, PERMANENT MEASURABLE GREEN COLOR IS DEVELOPED WITH CITRAL. QUANTITATIVE THIN LAYER CHROMATOGRAPHY WAS ALSO ADOPTED FOR DETERMINATION OF CITRAL IN VOLATILE OILS MAKING USE OF PROPOSED COLOR REACTION.|GAS CHROMATOGRAPHIC ANALYSIS OF CITRAL.|Method: AOAC 918.02; Procedure: colorimetric method; Analyte: citral; Matrix: lemon and orange extracts; Detection Limit: not provided.|Method: AOAC 963.17; Procedure: barbituric acid condensation method; Analyte: citral; Matrix: flavor extracts and toilet preparations; Detection Limit: not provided.

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