Isophytol

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.

Contain spills; may be ecotoxic at higher concentrations, hence do not allow to enter drains, surface water or groundwater; collect using inert absorbent and dispose of by incineration

Gel ointment containing 1% isophytol as the only terpene clearly enhanced percutaneous indomethacin absorption /of rat skin/ in comparison with gel ointment without any terpene, where no indomethacine was found in blood samples. However, the penetration-promoting effect of isophytol was relatively weak, clearly lower than any of the 7 tested monoterpenes, within the range of 4 tested sesquiterpenes; isophytol showed the lowest promoting effect of the 3 diterpenes to which group isophytol itself belongs.

Isophytol has a low acute oral and dermal toxicity: oral mammalian LD50 above 5000 mg/kg bw, with most values greater than 8000 mg/kg bw. The acute dermal LD50 is above 5000 mg/kg bw in rabbits. One intraperitoneal LD50 in mouse is 169 mg/kg bw. Inhalative tests over 8 hours in rodents show no effect of a nonaerosol isophytol-enriched atmosphere (NOEC about 0.3 mg/cu m based on vapor pressure). Isophytol is irritating to the skin, based on animal studies, but a 10% solution in petrolatum was not irritating to human volunteers. Isophytol is a slight eye irritant. In rabbit transient irritant reactions of the eyes were produced, which all resolved within 8 days. In two sensitization tests the reactions were judged to be of an irritant rather than a sensitizing nature, a maximization test with 10% isophytol in human volunteers was negative. The 28-day subchronic oral NOEL is 250 mg/kg bw/d, with only minor and reversible effects (including kidney weight changes) at the LOAEL of 1000 mg/kg bw/d. Based on histopathological data from a one-generation study with an average exposure of 64 days for females and of 98 days for males, the NOEL and NOAEL for parental systemic toxicity was below 250 mg/kg bw/d. Isophytol was not mutagenic in two bacterial tests, whereas one bacterial test was predominantly negative with a few ambiguous results. In an in vivo micronucleus test no clastogenic effects were seen. Thus isophytol is considered to be not mutagenic. There are no proper carcinogenicity data. In a one-generation reproductive toxicity study, 250 mg/kg bw/d was the LOAEL for parental toxicity based on effects in kidney (dilated renal tubules; renal mineralization). 500 mg/kg bw/d was the NOAEL for maternal reproductive effects based on a slightly increased mean pre-coital time, a decreased fertility index and conception rate. Postnatal loss was observed at low and medium dose (2% in controls, 7% at 250, 8% at 500 mg/kg bw/d) an increase of 39% at 1000 mg/kg bw/d was observed where also clinical signs in the mothers appeared. A NOAEL of 500 mg/kg bw/d was derived for developmental toxicity of the pups based on clinical signs and decreased body weight during the lactation period. In conclusion, the overall mammalian toxicity of isophytol is considered to be low but, based on animal data, there is a potential for irritation.

/AQUATIC SPECIES/ In a static test without emulsifier over 96 hours, isophytol caused no observable effects in Leuciscus idus (golden orfe) up at nominal concentrations of 5,000 and 10,000 mg/L. THE NOEC was 10,000 mg/L nominal concentration, which indicates that at natural solubility isophytol is not toxic to the fish.

/AQUATIC SPECIES/ The potential of isophytol for deterrence of /Balanus amphitrite (barnacle)/ larvae settlement was tested ... . Isophytol was dissolved in pure (99.7%) ethanol at various concentrations and an aliquot of 0.5 mL of this ethanol solution was added to treatment Petri dishes of 9 sq cm surface area; then, the solvent was left to evaporate. Concentrations of isophytol were selected to result in test substance concentrations of 0.01 to 10.0 g/sq cm Petri dish surface. ... Settlement tests were conducted by adding 25-35 mature free-swimming cypris larvae to the test vessels and incubating for 24 hours at 28 °C in a 15/9-hour light/dark cycle. ... The endpoint is the number of settled larvae per total number of larvae added. ... Pure isophytol was significantly deterrent at concentrations of 10 and 1 ug/sq cm ... The minimal inhibitory concentration for isophytol was calculated as < or = 1 ug/sq cm. ...

/OTHER TERRESTRIAL SPECIES/ Male and female rice leaf folder moths, the food specialist Marasmia patnalis and the generalist Cnaphalocrocis medinalis from the same family, were used to record electroantennograms in the presence of defined volatile chemicals of plant origin. ... The response ... to 91 volatile plant chemicals was similar to all compounds except three monoterpenes and two sesquiterpenes, including isophytol. The response of the food specialist Marasmia patnalis, that feeds on relatively few plants, most notably rice, to these substances was higher in comparison with the generalist Cnaphalocrocis medinalis. Further, while in M. patnalis both males and females showed similar electroantennographic reactions to isophytol, in C. medinalis the males showed a much stronger (but not statistically significant) reaction than the females. ... Isophytol may work as a volatile plant-derived semiochemical for (at least) these moths, allowing them in conjunction with other semiochemicals to locate certain plant species for food or mating/egg-laying purposes. The pronounced difference in reaction to isophytol in food-generalist C. medinalis males and females, with higher albeit non-significant reaction males, may additionally hint that isophytol, among other positive substances, may serve as a long-range attractant for males locating the females' host habitat.

/OTHER TERRESTRIAL SPECIES/ ... Even at a very high loading of 15000 mg isophytol per kg artificial sediment (dry weight), no effects on growth, egg production or fertility were observed /in Caenorhabditis elegans (roundworm)/. ...

For more Ecotoxicity Excerpts (Complete) data for ISOPHYTOL (6 total), please visit the HSDB record page.

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=505-32-8][Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=505-32-8]

Isophytol had previously been detected in dichloromethane extracts of the marine red alga Plocamium costatum.

Isophytol was detected at a concentration of 0.83% (area-%) in epicuticular leaf waxes of non-aphid-infested barley /(Hordeum vulgare L. cv. Aramir)/. It was not detected in the same leaf waxes of aphid-infested barley; however, in the latter, nearly the identical concentration (0.81%) of phytol was detected, which was not present on the surface of non-infected leaves. Isophytol was detected at a concentration of 1.40% (area-%) in methanol extracts of leaves of non-aphid-infested barley. It was not detected in the same methanol leaf extracts of aphid-infested barley; however, in these methanol extracts no phytol was detected, nor any other compound of the same concentration. No isophytol was detected in ethyl acetate extracts of non-aphid-infested nor of infested barley leaves. ... Isophytol is present in the epicuticular wax and within the leaf tissue of barley. Subsequent to infestation by aphids the isophytol disappears; while the epicuticular-wax isophytol may isomerise to phytol, which is found at similar concentrations in infested plants, the leafy-tissue isophytol seems to either dissipate, volatilize or be metabolised without obvious metabolites.

/HUMAN EXPOSURE STUDIES/ ... /In a maximization test/ ... 27 healthy, male and female volunteers /were subjected to/ ... five 48-hour induction applications to the same site on the forearm under occlusion and subsequent challenge on fresh sites after 10-14 days. /10% isophytol in petrolatum/ produced no significant reactions ... .

/ALTERNATIVE and IN VITRO TESTS/ Retinol-binding protein (RBP) is a blood protein specific for vitamin A (retinol) transport. RBP is excreted in the urine of patients of certain diseases. RBP was purified from such urine and the relative binding to RBP of vitamin A derivatives and selected terpenes with structural similarities to parts of retinol, as well as a long-chained (C10) alcohol and a long-chained (C17) fatty acid, was determined. ... In comparison with the retinol standard, RBP pre-exposure to isophytol resulted in only 39% retinol binding, respectively 61% retinol-binding inhibition. ... Among terpenoids, competitive binding was only higher in beta-ionone and beta-ionylidene acetic acid on one hand, both of which are characterized by a closed beta-ionone ring identical to the one in retinol, and by citral and pseudoionone, both of which have a terminal respectively subterminal carbonyl group. Competitive binding of phytol, an isophytol isomer with a terminal carboxyl group, was much lower than of isophytol (29% vs 61%). ...

/LABORATORY ANIMALS: Acute Exposure/ Rats, mice and guinea pigs /were exposed/ to a non-aerosol isophytol-enriched atmosphere for 8 hours at 20 °C, by bubbling water-vapor-saturated air through a 5-cm-thick layer of isophytol into the test cages. No effects were observed ... . Assuming the atmospheric isophytol partial pressure to correspond to the vapor pressure, this result translates to a calculated NOEC of 0.3 mg/cu m ... .

/LABORATORY ANIMALS: Acute Exposure/ ... In /a/ ... skin sensitization test ... 6/10 control (non-induced) guinea pigs showed positive reactions to 25% v/v isophytol in ethanol and a further 2/10 control animals showed positive reactions to 12.5% isophytol in ethanol; these reactions were considered by dermatoxicologists to be signs of primary irritation caused by isophytol.

/LABORATORY ANIMALS: Acute Exposure/ ... Undiluted /isophytol applying to rabbit skin caused/ severe erythema and heavy edema at 24 hours, heavy erythema and heavy flaking of skin at 8 days. /From table/

/LABORATORY ANIMALS: Acute Exposure/ ... Isophytol caused transient effects ... (light reddening of the eye at 1 hour and light reddening and dulling of the eye at 24 hours) after a single application of 50 uL of undiluted isophytol to rabbit eyes; these reactions resolved completely and there were no observed effects at 8 days after application ... .

For more Non-Human Toxicity Excerpts (Complete) data for ISOPHYTOL (14 total), please visit the HSDB record page.

Genetic toxicology testing has been performed with Salmonella typhimurium strains TA1535, TA100, TA97 and TA98 with and without S9 activation in 95% ethanol vehicle control. The results were inconclusive. In another study with Salmonella strains TA1535, TA97, TA100, TA104, TA98 and TA102 with DMSO as the vehicle, isophytol was negative in the presence or absence of S9 metabolic activation.

LD50 Rat oral > 8000 mg/kg /From table/

LD50 Rat oral > 12000 mg/kg /Isophytol crude/ /From table/

LD50 Mouse oral > 8000 mg/kg /From table/

LD50 Mouse ip 169 mg/kg /From table/

LD50 Rabbit dermal > 5000 mg/kg /From table/