4-methyl-3-decen-5-ol

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

25

Absorption rate - inhalation (%):

100

Additional information

No toxicokinetic studies are available that directly address absorption, distribution, metabolism, or excretion of 4-methyl-3-decen-5-olfollowing oral administration; however information is available from existing toxicology studies and the physical chemical properties to infer potential toxicokinetic properties. The extent of dermal absorption through human skin was determined in a fully compliant in vitro study, performed according to OECD 428.

Toxicological end points for4-methyl-3-decen-5-ol

Acute oral toxicity (mouse)	LD50 >8000 (united not reported; mg/kg bw assumed)
Acute dermal toxicity	LD50 >5000 mg/kg
Acute IP toxicity (mouse)	1000 < LD50 < 2000 (units not reported; mg/kg bw assumed)
In vivo skin irritation	Non irritant
In vivo eye irritation	Non irritant
Skin sensitisation (OET)	Not a skin sensitiser
Skin sensitisation (HRIPT)	Not a skin sensitiser
In vitro gene mutation/Ames	Negative
In vitro cytogenicity	Negative
Micronucleus	Negative
Repeat dose (16 week, diet)	NOAEL 10000 ppm
Repeat dose (27 week, diet)	NOAEL 1000 ppm
Reproduction/developmental screening test (OECD 421), dermal	0, 50, 150 and 300 mg/kg bw/day NOAELs parental systemic = 300 mg/kg bw/day reproduction = 300 mg/kg bw/day developmental = 300 mg/kg bw/day
In vitro dermal absorption
Bioaccumulation factor	174 L/kg

 

Significance of routes of exposure 

Oral route: this is not considered a relevant route for occupational exposure or for the general population. Slight exposure may occur via accidental hand-to-mouth contact, but this is not expected to contribute significantly to exposure.

 

Inhalation route: the substance has a low vapour pressure and a high boiling point and therefore is unlikely to volatilize or be released into the air. Under conditions of normal handling and use, the substance will not be aerosolized. Water solubility is low and this can enhance penetration to the inner respiratory tract however, absorption would occur mainly via micellular solubilisation because the high lipophilicity.

 

Dermal route:this is considered to be the principal route for occupational exposure, and also for exposure of the general population.

 

Absorption

The main physical chemical properties that influence absorption are molecular weight, and water and lipid solubility. The substance has a molecular weight of 170, a water solubility of 63 mg/L at 20°C and Log Kow of 3.9. All these properties suggest 4-methyl-3-decen-5-ol would be absorbed by the gastro-intestinal tract following oral exposure and become systematically available because the substance is able to dissolve to some extent and permeate the cell membrane. Acute oral toxicity study showed low inherent systemic toxicity.

 

Based on the low vapour pressure (1.1 Pa at 25°C) 4-methyl-3-decen-5-ol is unlikely to volatilize or be released into the air. However, the moderate water solubility and optimal Log Pow indicate inhalation as another possible route of absorption. It is likely that4-methyl-3-decen-5-olwill be absorbed if inhaled, based on available toxicity data showing a degree of bioavailability after oral exposure. As a worst-case assumption, inhalation absorption of 4-methyl-3-decen-5-ol is considered high for risk assessment purposes.

 

Dermal absorption is also likely, because 4-methyl-3-decen-5-ol is a liquid, molecular weight is not excessive and lipophilicity appropriate for allowing the substance to cross the stratum corneum of the skin. On the other hand, water solubility suggests that permeation through the stratum corneum into the epidermis would be low to moderate.

 

The results of the acute dermal toxicity study performed in rabbits, the skin of which are known to be more permeable than that of rats, thus even more permeable than human skin (US EPA Dermal Exposure Assessment: Principles and Applications EPA/600/8-91/011B January 1992 Interim Report) confirms that 4-methyl-3-decen-5-ol possess low toxicity also following dermal exposure, with the LD50 value obtained in this study was in excess of 5000 mg/kg. Repeat-dose dermal studies in rats with an analogous substance also showed no evidence of systemic toxicity at dose levels up to 450 mg/kg bw/day. For purposes of risk assessment, a default value for dermal penetration is assumed (25%) .

 

Distribution 

Any 4-methyl-3-decen-5-ol that is absorbed will be distributed via the blood to the liver and other organs and tissues.No target organs are identified from toxicity studies; the bioconcentration factor is calculated to be moderate so no marked bioaccumulation is expected.  

 

Metabolism and potential for bioaccumulation

Based on its chemical structure,4-methyl-3-decen-5-ol may be metabolized at least via oxidative metabolism. Due to the small molecular size, it is feasible that elimination will be quite rapid via urine, thus limiting the degree of metabolism. Metabolism may therefore be incomplete.

The structure of the substance provides information that helps predicts the probable metabolic pathways. The OECD Toolbox (version 2.3) liver, skin, and microbial metabolism simulators predict 63 metabolites for the liver, 4 metabolites for the skin and 103 metabolites for microbial metabolism. The structure of liver metabolites suggests that changes would involve mainly the side-chain, which will be subjected to beta-oxidation, and most of the 63 liver metabolites are likely to represent intermediate metabolites. As the side chain contains odd number of carbon (9-11), propionyl-CoA in addition to acyl-CoA would be produced. Both will enter into the citric acid cycle and form a source of energy. It is expected that the terminal metabolite obtained after the side chain has been metabolized, can be conjugated and excreted. Considering the number of metabolites the OECD Toolbox predicted for microbial metabolism, any unabsorbed substance is expected to be extensively metabolised by the intestinal microflora. 

 

Excretion 

No evidence of substance retention or bioaccumulation is predicted, or seen in toxicity studies. Low, molecular weight (below 200) suggests that excretion will be mainly via the urine, and may be rapid. The same would occur for metabolites generated by the liver. Although toxicity including mortality is reported in acute studies, no duration of symptoms or time of death is reported so rapidity of elimination cannot be supported by experimental data.

 

In summary 

4-methyl-3-decen-5-ol is inferred to be well absorbed following oral exposure, highly absorbed following inhalation exposure and poorly absorbed following dermal exposure. The absorbed 4-methyl-3-decen-5-ol will be distributed within the body, and metabolised to some extent by the liver. It is not expected that 4-methyl-3-decen-5-ol will bioaccumulate. The urine is likely to be the main route of excretion.