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1-Dodecanol [MAK Value Documentation, 2006]

Published Online: 31 JAN 2012

DOI: 10.1002/3527600418.mb11253kske0022

The MAK Collection for Occupational Health and Safety

The MAK Collection for Occupational Health and Safety

How to Cite

2012. 1-Dodecanol [MAK Value Documentation, 2006]. The MAK Collection for Occupational Health and Safety. 117–132.

Publication History

  1. Published Online: 31 JAN 2012
MAK valuenot yet established, see Section IIb of the List of MAK and BAT Values
Peak limitation-
Absorption through the skin-
Sensitization-
Carcinogenicity-
Prenatal toxicity-
Germ cell mutagenicity-
BAT value-
Synonymsdodecyl alcohol lauryl alcohol
Chemical name (CAS)1-dodecanol
CAS number112–53–8
Structural formula
original image
Molecular formula 
Molecular weight186.38
Melting point26°C
Boiling point264.6°C
Density at 24°C0.8309 g/cm3
Vapour pressure at 20°C< 0.02 hPa
log Pow*5.16–5.36
1 ml/m3 (ppm)7.73 mg/m31 mg/m30.129 ml/m3 (ppm)
Solubility (at 20°C)insoluble in water, soluble in ethanol and ether (Rowe and McCollister 1982)
Purity, impuritiesin addition to 65 % 1-dodecanol, commercially available batches can
  1. a

    *n-octanol/water distribution coefficient

 contain up to 20 % 1-tetradecanol, 10 % 1-hexadecanol and 5 % 1-octadecanol or may be 95–99 % pure (ECB 1998, Egan and Portwood 1974)
Stabilityoxidatively stable with atmospheric oxygen under normal conditions and the absence of light (Noweck and Ridder 1987)
Productionsaponification of coconut oil and subsequent hydrogenation at high pressure (Noweck and Ridder 1987, Rowe and McCollister 1982), Ziegler process (Egan and Portwood 1974)
Usesadditive for metal working fluids (≤ 5 %), lubricant additive (cold rolling oils, bearing lubricating oils, hydraulic oils) (ECB 1998), emulsifier in antirust emulsions (Förster et al. 1988)
starting material for the production of tensides, emulsifiers, wetting agents and cosmetics; solvent, foam stabilizer, component of cosmetics (ECB 1998)
wool wax alcohol

1 Toxic Effects and Mode of Action

  1. Top of page
  2. Toxic Effects and Mode of Action
  3. Mechanism of Action
  4. Toxicokinetics
  5. Effects in Humans
  6. Animal Experiments and in vitro Studies
  7. Manifesto (MAK value/classification)
  8. References

The acute oral and dermal toxicity of 1-dodecanol is very low. Damage to organs has not been observed. Depending on the solvent used, 1-dodecanol is absorbed poorly to well through the intact mouse skin. The dermally absorbed substance is excreted mainly with the exhaled air as carbon dioxide. The undiluted substance is barely irritative in man after single applications. In the guinea pig and the hairless mouse, the irritation after single applications of the substance is likewise slight, but in the rabbit, the most sensitive species, it is moderate. After repeated contact, somewhat stronger skin irritation can occur. Irritation of the mucous membranes was slight in animal experiments, as was the sensitization potential. In the Salmonella mutagenicity test, 1-dodecanol was not mutagenic. In the micronucleus test in vivo, 1-dodecanol was not found to have an effect. In a one-generation study, 1-dodecanol did not have adverse effects on reproduction. 1-Dodecanol is a co-carcinogen for benzo[a]pyrene in the mouse. The tumour-promoting effects on the mouse skin are, despite the irritation, negligible.

2 Mechanism of Action

  1. Top of page
  2. Toxic Effects and Mode of Action
  3. Mechanism of Action
  4. Toxicokinetics
  5. Effects in Humans
  6. Animal Experiments and in vitro Studies
  7. Manifesto (MAK value/classification)
  8. References

Like other longer-chain alcohols (Benane et al. 1993, McCreery and Hunt 1978, Jaworska and Schultz 1993, Lipnick et al. 1985, Rang 1960), as a result of its hydrophilic and lipophilic properties, 1-dodecanol probably affects cell membranes in an unspecific manner.

3 Toxicokinetics

  1. Top of page
  2. Toxic Effects and Mode of Action
  3. Mechanism of Action
  4. Toxicokinetics
  5. Effects in Humans
  6. Animal Experiments and in vitro Studies
  7. Manifesto (MAK value/classification)
  8. References

3.1 Absorption, distribution, elimination

Three groups of 21 Sprague-Dawley rats were exposed to an aerosol of 1-dodecanol at a concentration of 1050 mg/m3 for 6 hours. The mass median aerodynamic diameter was 2.98 µm with a geometric standard deviation of 2.5 µm. The average concentrations of 1-dodecanol in the lungs were between 23.1 and 27.1 µg/g. With further exposures for 1, 6 or 18 hours, concentrations were detected in the lungs of 6.5 ± 2.3, 48.7 ± 3.7 and 200 ± 23 µg/g lung (Ulrich and Marold 1979).

After occlusive dermal exposure to 0.5 % [1-14C]-1-dodecanol in triethyl citrate for 24 hours, 2.84 % was absorbed. 95 % of the dose was recovered from the site of application. 0.1 % of the dose was detected in the faeces and 0.13 % in body tissue. In the exhaled air 2.61 % was detected as CO2, corresponding to 91 % of the absorbed radioactivity. In the skin at the site of application 0.6 % of the applied dose was found in the horny layer, and 1.15 % in the rest of the skin without horny layer. The influence of the solvent and substance concentration on absorption was also investigated. While absorption of the substance from triethyl citrate and castor oil at all tested concentrations was low (> 0.05 %), similar to that of the undiluted substance, absorption from squalene at low concentrations (0.05 %) was about 3 to 5 times higher than with the other two solvents or the undiluted substance. At higher concentrations absorption from squalene decreased (Iwata et al. 1987).

On the other hand, after epicutaneous exposure for 4 hours to 1.38 µmol [1-14C]-1-dodecanol in 25 µl ethanol, a hairless mouse absorbed 46.1 ± 0.9 % of the dose applied to 2.9 cm2 dorsal skin under occlusion. 1.2 ± 0.2 % of the applied dose was found in the faeces and urine, 27.2 ± 1.0 % was exhaled. 17.7 ± 1.9 % was found in the body at autopsy 4 hours after application. 52.9 ± 2 % of the administered radioactivity was recovered from the excised skin at the site of application (Nishiyama et al. 1983).

3.2 Metabolism

1-Dodecanol is probably oxidized via the aldehyde and acid to CO2 (see also Section 3.1; Iwata et al. 1987, Williams 1959). Hydroxylation in ω and (ω-1) position and oxidation to lauric acid was detected in frog liver microsomes (Miura 1981).

4 Effects in Humans

  1. Top of page
  2. Toxic Effects and Mode of Action
  3. Mechanism of Action
  4. Toxicokinetics
  5. Effects in Humans
  6. Animal Experiments and in vitro Studies
  7. Manifesto (MAK value/classification)
  8. References

There are no data available for the effects of 1-dodecanol in humans after single and repeated exposures.

4.1 Local effects on skin and mucous membranes

Slight irritative potential was detected for 1-dodecanol only in one 24-hour patch test with Japanese persons (see Table 1; Sato et al. 1996). This could not be verified in other patch tests (Basketter 1997, Henkel 1996, ästner 1977, Opdyke 1973b). Likewise, no irritative reactions could be detected using Burckhardt's method with repeated non-occlusive application. Only in the Duhring chamber scarification test according to Frosch and Kligman was the substance classified as clearly irritative. With this test method, which was developed for testing weak irritants, the skin is abrased before the occlusive Duhring chamber is applied (Frosch and Kligmann 1976, 1977).

Table 1. Irritative effects of 1-dodecanol in humans
Test, duration of exposure, collectiveConcentration, vehicle, purityEffects or number of reactions (strength of the reaction), time of readingReferences
Test persons
patch test, semi-occlusive, 4 hundiluted0/29Basketter et al. 1997
patch test, semi-occlusive, 4 h positive controlundiluted 20 % sodium dodecyl sulfate in water0/20 4/20, only weak reaction, not significantly stronger than with 1-dodecanolHenkel 1996
patch test, occlusive, 24 h, outside upper arm50 % in petrolatum0/4, read after 24, 48 and 72 hKästner 1977
patch test, occlusive, 24 h0.5–2.0 M petrolatum (about 11 to 44 %)slight irritation (0–0.1 on a scale of 0 to 2), read after 1 hSato et al. 1996
repeated non-occlusive application, 60 × in 30 min to the same site on the forearm5 %, solvent not statedneither subjective complaints nor objective symptoms of irritationHenkel 1981b
patch test, occlusive, 48 h4 % in petrolatum0/25Opdyke 1973b
Duhring chamber scarification test, scarified skin, occlusive, 1×/day, 3 days, 5–10 healthy, young, pale-skinned Caucasians with a high tendency towards irritation25 % in mineral oil, controls: mineral oilmarked irritation (2.5–4 on a scale from 0–4), after 30 min not irritativeFrosch and Kligman 1976
Patients
patch test, occlusive, 40 consecutive patients of a dermatological clinic with eczema, but without allergy to ointment bases containing wool wax alcohol1 % in CCl4, purity not statednot primarily toxic (irritative)Peter et al. 1969

Another study with patch testing, in which there was no significant difference between the results of the positive controls (20 % sodium dodecylsulfate) and those of the test group, is not included in the evaluation as a result of this methodological shortcoming (Henkel 1996, 1999).

Skin irritation is to be expected after repeated use (dehydration dermatosis).

There is no information available about the effects on the mucous membranes.

4.2 Allergenic effects

In persons with healthy skin, there was no evidence of allergenic effects either in a maximization test or a patch test with a sufficiently high concentration in a suitable vehicle (Kligman 1966, 1998, Komamura et al. 1997, Opdyke 1973a, 1973b) (Table 2). In collectives of patients the percentage of reactions in patch tests varies depending on the test concentration (e.g. very high test concentration in Auth et al. 1984), vehicle and selection of the patients. The collectives of patients were either patients with contact dermatitis or patients with anamnestic or clinically manifest venous ulcers or stasis eczema of the lower leg. With the consecutive testing of patients with existing contact dermatitis of different genesis (Hjorth and Trolle-Lassen 1963, Peter et al. 1969) on the one hand the numerous reactions may have been induced by a reduced irritation threshold, which led to false positive reactions which were in fact irritative (Kligman 1998). On the other hand, in these consecutive test studies there are no data for the actual clinical relevance of the reactions found. In addition, the skin barrier is impaired in these patients, as a result of their illness, and facilitates the penetration of potential allergens and thus sensitization. In patients with a history of ulcers, the occlusive treatment with local therapeutic agents can play a role as well.

Table 2. Sensitizing effects of 1-dodecanol in humans
Test, duration of exposure, collectiveConcentrationa, vehicle, purityEffects or number of reactions (strength of the reaction); time of readingReferences
  1. a

    recommended test concentration: 20 % in petrolatum (Rietschel and Fowler 1995)

Test persons
maximization test4 % in petrolatum0/25Kligman 1966
Patients
patch test according to the ICDRG standard, 24 h, 51 (24 ♀/27 ♂)/171 patients of a dermatological clinic with positive results in patch tests to 30 % wool wax in petrolatum and contact dermatitis, mainly after the use of external therapeutic agents, and suspected sensitization to ointment bases30 % in petrolatum, purity not stated13/51 (1+), 9/51 (2+ or 3+), scale: 0 to 4+, clinically relevant; read after 24, 48 and 72 hAuth et al. 1984
patch test, consecutive dermatitis patients of a dermatological clinic with contact with topical cosmetic or medical preparations, no other details5 % in petrolatum 10 % in petrolatum purity > 95 %4/1664 15/1664 concentrations not irritative, no other detailsHjorth and Trolle-Lassen 1963
patch test, 48 h, patients of a dermatological clinic with suspected allergy to topical preparations, 108 ♀, 38 ♂5 % in petrolatum purity > 99 %0/146; read on days 2, 3 and 7Tosti et al. 1996
patch test, no other details, consecutive patients of a dermatological clinic with proven allergy to ointment bases containing wool wax alcohol1 % in carbon tetrachloride, purity not statedabout 16 % of 30 (48 h); unclear whether several readings taken to observe crescendo reactionsPeter et al. 1969
Case reports   
patch test, female patient with tinea pedis and ulcus cruris and for over two years contact dermatitis to topical medicines containing 1-dodecanol20 % in petrolatum, purity not statednegative results, no other detailsIshiguro and Kawashima 1991
patch test, 48 h, patient with itching lesions on an amputation stump after using a cream containing small amounts of 1-dodecanol23.1 % in petrolatum purity 99.6 %negative results; read after 48 and 72 hKomamura et al. 1997

To what extent impurities are responsible for reactions to 1-dodecanol cannot be seen from the studies available, as there are no details on purity in most publications.

5 Animal Experiments and in vitro Studies

  1. Top of page
  2. Toxic Effects and Mode of Action
  3. Mechanism of Action
  4. Toxicokinetics
  5. Effects in Humans
  6. Animal Experiments and in vitro Studies
  7. Manifesto (MAK value/classification)
  8. References

5.1 Acute toxicity

5.1.1 Inhalation

63 Sprague-Dawley rats were exposed to an aerosol of 1-dodecanol in a concentration of 1050 mg/m3 for 6 hours (see Section 3.1). Reduced activity was observed in all animals, and dyspnoea in some animals. All animals survived the treatment. Only in a few animals were slight, unconnected areas of lung haemorrhage seen at autopsy (only lungs and trachea) (Ulrich and Marold 1979).

5.1.2 Ingestion

The acute oral toxicity of 1-dodecanol is very low (Table 3). In a study with 7 rabbits and 7 rats which survived oral administration of technical grade 1-dodecanol in doses of up to 36 ml/kg body weight (29900 mg/kg body weight), gross pathological and microscopic examination of the organs did not yield unusual findings (no other details). In one rat, which died 6 days after oral administration of 36 ml/kg body weight, fatty degeneration of the liver and confluent bronchopneumonia were found (Rowe and McCollister 1982). In another study according to OECD test guideline 401, marked piloerection and slight sedation were observed about 20 minutes after gavage administration of 5000 mg/kg body weight in the form of an aqueous suspension. The symptoms had regressed completely 24 hours after administration of the substance. Other symptoms were not detected in either the first 24 hours, or 7 and 14 days after administration. All animals survived the treatment. Autopsy did not yield conspicuous findings in the inner organs and body cavities (Henkel 1981a).

Table 3. Acute oral toxicity of 1-dodecanol
 LD50 [mg/kg body weight]References
rat33220 (> 40 ml/kg body weight)Procter & Gamble 1999
rat >10600 (> 12.8 ml/kg body weight)Rowe and McCollister 1982
rat> 10600Lington and Bevan 1994
rat> 26500Egan and Portwood 1974, Noweck and Ridder 1987
rat >5000Henkel 1981a
mouse >3125Henkel 1981b
rabbit> 29900 (> 36 ml/kg body weight)Treon 1963
5.1.3 Dermal absorption

The LD50 after epicutaneous application of the substance to guinea pig skin was > 10 ml/kg body weight (8310 mg/kg body weight) (Rowe and McCollister 1982).

5.1.4 Other routes of absorption

After forced aspiration of 0.2 ml 1-dodecanol, 7/10 Sprague-Dawley rats died of pulmonary oedema within 7 to 30 minutes, one animal after 5 hours and another after more than 5 hours (compared with methanol 1/10 and ethanol 5/10 within a few minutes and 6.5 hours, respectively). The average lung weights were more than three times those of the untreated animals. Gross pathological examination revealed massive, extensive, severe bleeding in the lungs. The lungs were dark red like after the aspiration of kerosine (Gerarde and Ahlstrom 1966).

The LD50 after intraperitoneal administration of the substance to the rat is given as 800 to 1600 mg/kg body weight (no other details; Rowe and McCollister 1982).

5.2 Subacute, subchronic and chronic toxicity

5.2.1 Ingestion

Groups of 12 male and 12 female Wistar rats were given 1500, 7500 or 30000 mg 1-dodecanol (99 %) per kg diet (about 100, 500 and 2000 mg/kg body weight and day) for 8 weeks. During the study period there were no effects on body weight, food consumption and utilization, or the absolute and relative organ weights. Gross pathological and microscopic examination of the control and high dose groups did not reveal unusual findings in any of the animals. Additionally in the male animals, haematological and biochemical parameters were investigated in the blood. A dose-dependent decrease in the total number of leukocytes was determined at 500 and 2000 mg/kg body weight and day and in the triglyceride level at 2000 mg/kg body weight and day. A subsequent differential blood count did not reflect these changes. The NOAEL (no observed adverse effect level) in this study for the changes in the leukocyte count was 100 mg/kg body weight and day (Danish National Food Agency 1992).

One study, in which 10 % 1-dodecanol in the diet of male Wistar rats caused the death of all animals after 12 days while 5 % 1-dodecanol was tolerated well, is not included in the evaluation as the only parameters investigated were body weight gains and lethal toxicity, and there were not enough animals used (no other details; Yoshida et al. 1971).

5.2.2 Intraperitoneal injection

An intraperitoneal dose of 500 mg/kg body weight was found to be the maximum tolerated dose in a dose-finding study for a short-term carcinogenicity test (Section 5.7), in which 15 A/He mice per dose group and sex were injected with a solution of 1-dodecanol in redistilled tricaprylin 3 times a week over a period of 8 weeks. The organs included in the microscopic and gross pathological examinations were the lungs, liver, kidneys, spleen, thymus, intestine, and salivary and endocrine glands (no other details; Stoner et al. 1973).

There are no data available for the effects of 1-dodecanol after inhalation of the substance.

5.3 Local effects on skin and mucous membranes

5.3.1 Skin

The irritative effects of 1-dodecanol after single applications of the substance to the skin are slight (Table 4). The rabbit as the most sensitive species reacted to undiluted 1-dodecanol with slight to moderate skin irritation. While even 50 % 1-dodecanol in petrolatum was still moderately irritative in the rabbit, guinea pigs and the hairless mouse produced only slight irritation in a few cases in the same investigation. This very different sensitivity between the various species may be explained by the different permeability of the skin (Bartek et al. 1972, Hopf 1971, 1971ästner 1977, Motoyoshi et al. 1979, Phillips et al. 1972).

Table 4. Irritative effects of 1-dodecanol on the skin of rabbits, guinea pigs, rats and hairless mice
Species, test, site of application, duration of actionConcentration, vehicle, purityEffects (strength of the reaction); time of readingReferences
  1. a

    Evaluated according to OECD: PII (primary irritation index): 0–0.5 not irritative, 0.6–3.0 mildly irritative, 3.1–5.0 moderately irritative, 5.1–8.0 strongly irritative

Single applications   
Rabbit   
Draize test, 24 hnot statedmoderately irritative (PIIa4.6/8)Procter & Gamble 1999
patch test, 24 h, shaved dorsal skin50 % in petrolatummoderately irritative, score: 4/5; 24, 48 and 72 h after applicationKästner 1977
FDA method,undilutedPIIa2.9/8Iwata et al.
occlusive, 24 h50 % in squalenePIIa1.7/81987
 50 % in castor oilPIIa0.6/8 
 50 % in triethyl citratePIIa1.4/8 
  all mildly irritative; 1, 24 and 48 h after application, evaluated according to OECD test guideline 404 
patch test, 4 h5 %, solvent not statedmildly irritativeHenkel 1981b
Guinea pig   
patch test, 24 h, shaved dorsal skin50 % in petrolatumonly in some animals slight, rapidly regressing reactions, score 2/5, slight irritation; 24, 48 and 72 h after applicationKästner 1977
Hairless mouse   
patch test, 24 h, dorsal skin50 % in petrolatumonly in some animals slight, rapidly regressing reactions, score 2/5, slight irritation; 24, 48 and 72 h after applicationKästner 1977
FDA method,undilutedPIIa2.1/8Iwata et al.
occlusive, 24 h50 % in squalenePIIa1.8/81987
 50 % in castor oilPIIa1.2/8 
 50 % in triethyl citratePIIa1.3/8 
  all mildly irritative; 1, 24 and 48 h after removal of the plaster, evaluated according to OECD test guideline 404 
Repeated application
Rat
8 weeks, no other detailsundiluted 100, 500 or 2000 mg/kg body weightabrasion of the skin, no other detailsDanish National Food Agency 1992
Hairless mouse
2 ×/day, 10 workdays, no solvent control5 %, no other detailsmild irritation; 24, 48 and 72 h after applicationHenkel 1981b

In the rat, also a sensitive species with much greater permeability of the skin than humans, marked damage to the skin was observed after repeated application of undiluted 1-dodecanol (Bartek et al. 1972, Rieger et al. 1964).

5.3.2 Eyes

The irritative effects of the substance in the rabbit eye according to Draize were slight after the use of undiluted 1-dodecanol and mixtures of 1-dodecanol with 1-tetradecanol (Table 5).

Table 5. Irritative effects of 1-dodecanol on the rabbit eye
TestConcentration, vehicle, purityEffectsReferences
  1. a

    Evaluated according to OECD: PII (primary irritation index): 0–10 not irritative; 11–25 mildly irritative; 26–56 moderately irritative; 57–110 strongly irritative

OECD test guideline 405undiluted, technical gradenot irritativeHenkel 1988
Draize test, no other details 26.7/110, moderately irritativeaProcter & Gamble 1999
Draize test, unrinsed rabbit eye70 % with 30 % 1-tetradecanolbarely perceptible reddening of the conjunctiva, 2 and 6 h, but not 24 h after instillationHenkel 1980
Draize test 0.1 ml1-dodecanol and 1-tetradecanol1 h: 9.3/100; not irritativeProcter & Gamble 1999
Draize test, no other details5 %, solvent not statedslightly irritative, 2 and 24 h after instillation: conjunctival reactions less than 10 % of the maximum possible reaction, 48 h after instillation: conjunctiva normal, cornea and iris normal at all timesHenkel 1981b

5.4 Allergenic effects

The sensitization potential of a 1-dodecanol mixture before and after hydrogenation (see “Production”) was tested on guinea pigs previously sensitized with the raw material (no other details). The 1-dodecanol mixture before hydrogenation, in an aqueous vehicle, did not produce skin reactions in the patch test (concentration 0.33 %, 6 hours, read after 24 and 48 hours) in any of the 5 pre-sensitized animals. A solution of the 1-dodecanol mixture before hydrogenation, in 80 % aqueous ethanol vehicle, produced a reaction in 3 of 5 animals (concentration 0.33 %, 4 hours, read after 24 and 48 hours). Under these conditions, 1-dodecanol after hydrogenation also caused cross-reactions (Procter & Gamble 1999).

5.5 Reproductive toxicity

In a one-generation study, 99 % 1-dodecanol was given to male and female Wistar rats with the diet in doses of 100, 500 or 2000 mg/kg body weight and day for 14 days. In the study period of 8 weeks, the incidence of pregnancy was not significantly changed, nor was the duration of pregnancy. On days 1 to 5 after birth, the number of offspring per litter, the weight of the offspring, and the distribution of the sexes and number of live births corresponded to those of the untreated control group (Danish National Food Agency 1992).

5.6 Genotoxicity

5.6.1 In vitro

1-Dodecanol was not found to be mutagenic in the Salmonella mutagenicity test with strains TA98, TA100, TA1535, TA1537 and TA1538 in the presence and absence of a metabolic activation system (S9 fraction from the livers of rats treated with Aroclor 1254) in concentrations of 4, 20, 100, 500 or 2500 µg/plate as a suspension in water using Tween 80. After doses of 100 µg/plate or more, 1-dodecanol had toxic effects (Henkel 1982).

90 % 1-dodecanol was not found to be mutagenic in the Salmonella mutagenicity test with strains TA98, TA100, TA1535, TA1537 and TA1538, and Escherichia coli (WP2uvrA) in the presence and absence of a metabolic activation system (S9 fraction from the livers of rats treated with polychlorinated biphenyls (KC 500)) in concentrations of 0.01, 0.05, 0.1, 0.5 1, 5, 10 or 50 µg/plate in DMSO. With strain TA1535 growth inhibition was observed after concentrations of 10 µg/plate or more, with the other strains after 50 µg/plate or more (Shimizu et al. 1985).

5.6.2 In vivo

In a micronucleus test according to OECD test guideline 474, no significant increase in the incidence of micronuclei was observed after mice were given gavage doses of 1-dodecanol of 5000 mg/kg body weight in arachis oil. The batch investigated was 100 % pure. Neither an increase in mortality nor a decrease in the ratio of polychromatic to normochromatic erythrocytes was observed (Henkel 1992).

5.7 Carcinogenicity

After the application of 1 drop (about 20 µl) of a 20 % solution of 1-dodecanol (purity determined gas chromatographically to be 97 %, impurities mainly homologues) in cyclohexane 3 times a week for a period of 60 weeks to mouse skin previously initiated with dimethylbenz[a]anthracene, a papilloma developed in 2/30 mice after 39 and 49 weeks, respectively. No papillomas developed in the non-initiated control. The dose per application was 160 mg/kg body weight. The skin at the site of application was severely irritated up to week 12 of the study, but returned to normal after week 20. The observed effects were weak compared with those of other substances, including known tumour promotors or strongly irritative substances. Statistical significance was not given. The low incidence of these tumours is unlikely, however, to be significant. There are no data for only initiated animals (Gilbert and Sicé 1960, Sicé 1966).

Groups of 20 C3H/He mice were exposed epicutaneously twice a week to 50 mg of a solution of 0.05 or 0.2 % benzo[a]pyrene in decalin containing 0, 10, 20, 30, 40, 50, 75 or 100 % 1-dodecanol. The time until malignant skin tumours developed became shorter with increasing dose: with 0.05 % benzo[a]pyrene in 1-dodecanol (100 %) the first tumours developed after 26 weeks, while with 0.05 % benzo[a]pyrene in decalin without 1-dodecanol a latency period of 63 weeks was observed. In the 0.2 % benzo[a]pyrene group the latency period in animals not exposed to 1-dodecanol was 42 weeks and in those exposed to 100 % 1-dodecanol 22 weeks. This co-carcinogenic effect was the most marked at low concentrations of benzo[a]pyrene (0.05 %) and 1-dodecanol (10 and 20 %). Neither exposure to 50 % 1-dodecanol in decalin without benzo[a]pyrene nor exposure to 0.002 % benzo[a]pyrene in decalin caused development of skin tumours in the animals (Bingham and Falk 1969).

The skin of 50 female ICR/Ha-Swiss mice was painted three times a day over a period of 440 days with 5 µg benzo[a]pyrene/0.1 ml acetone with and without 10 mg 1-dodecanol purified by distillation. In 21 mice 27 papillomas developed and in 13 mice squamous cell carcinomas. Application of benzo[a]pyrene alone induced 26 papillomas in 16 mice and squamous cell carcinomas in 12 mice. While the first papilloma developed in the animals treated with benzo[a]pyrene and 1-dodecanol after 226 days, the first developed in the group treated only with benzo[a]pyrene after 210 days. None of the 50 animals exposed to 1-dodecanol alone developed tumours. In this study, therefore, 1-dodecanol had no effect on the absolute number of tumours (27 papillomas and 13 squamous cell carcinomas compared with 26 and 12 in the initiated solvent control group), while the number of animals with papillomas in the group treated with 1-dodecanol was increased (21 compared with 16). The papillomas developed later, however. In the opinion of the authors of the study, 1-dodecanol is a weak to moderate co-carcinogen (Van Duuren and Goldschmidt 1976).

In a carcinogenicity screening test for lung adenomas according to Shimkin, groups of 15 A/He mice per sex and dose were given intraperitoneal injections of 1-dodecanol of 100 or 500 mg/kg body weight in tricaprylin 3 times a week for 8 weeks. No increase in lung tumours was observed at the end of the study 24 weeks after the first injection (Stoner et al. 1973). This method is, however, not a usual test, as it is substance class-specific and not a validated carcinogenicity bioassay.

5.8 Other effects

15 Wistar rats were given daily gavage doses of 1-dodecanol of 4 ml/kg body weight (3300 mg/kg body weight) for a period of ≥ 2 months. 4 animals were autopsied. After a month, some hepatocytes were observed with small mitochondria and poorly developed cristae, while others had enlarged mitochondria with well-developed cristae. Other microscropic effects were proliferation of the smooth endoplasmic reticulum and an increase in the number of lysosomes and microbodies (Wakabayashi et al. 1991).

A study of the influence of intraperitoneally administered 1-dodecanol on the lifespan of mice with Ehrlich ascites cell transplants is not included in the evaluation as too few animals were used (n = 4/group) (Ando et al. 1972).

6 Manifesto (MAK value/classification)

  1. Top of page
  2. Toxic Effects and Mode of Action
  3. Mechanism of Action
  4. Toxicokinetics
  5. Effects in Humans
  6. Animal Experiments and in vitro Studies
  7. Manifesto (MAK value/classification)
  8. References

Results of studies of exposed persons which would be suitable for the derivation of a MAK value are not available. Studies with repeated inhalation exposure are also lacking. The NOAEL found in an 8-week feeding study with the rat was 100 mg/kg body weight and day. This NOAEL is deduced from a dose-dependent decrease in the total number of leukocytes, which was not reflected in the differential blood count. It cannot be excluded that the local effect of 1-dodecanol is the most sensitive endpoint. As a result of the lack of information on this, no MAK value can be established. The substance is classified in Section IIb of the List of MAK and BAT Values. As 1-dodecanol caused slight irritation to the skin and eye and slight systemic toxicity with repeated exposures, health hazards are not to be expected at workplaces where metal working fluids are used provided the technically based threshold limit of 10 mg/m3 is observed.

Designation with “Sh” is not justified, as 1-dodecanol is very probably an unimportant allergen. On the one hand, only relatively few cases have been observed despite the widespread use of the substance; on the other hand, studies are available from several independent centres, but mainly without clinically relevant data. In addition, the observed sensitization was mainly connected with previous illness, namely anamnestic or clinically manifest stasis eczema of the lower leg or venous ulcers. Valid animal experiments are not available. There is also no information available about the sensitizing effects on the airways.

Designation with “H” is not justified. 1-Dodecanol is absorbed through the skin, but its dermal toxicity is low.

References

  1. Top of page
  2. Toxic Effects and Mode of Action
  3. Mechanism of Action
  4. Toxicokinetics
  5. Effects in Humans
  6. Animal Experiments and in vitro Studies
  7. Manifesto (MAK value/classification)
  8. References
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