Dodecan-1-ol

Endpoint summary

Description of key information

The key acute oral toxicity study for dodecan-1-ol, conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an LD50 value of >2000 mg/kg bw in rat (Safepharm Laboratory, 1996; rel 1).

There are no acute inhalation toxicity data for dodecan-1-ol. Therefore data are read-across from decan-1-ol and tetradecan-1-ol.

The acute inhalation toxicity study with decan-1-ol, conducted prior to OECD Test Guideline and GLP, reports an LC50 of >71mg/L in rats, following 1-hour whole body inhalation exposure to the atmosphere generated as a mist (Scientific Associates 1977; rel 2).

The acute inhalation toxicity study with tetradecan-1-ol, conducted prior to OECD Test Guideline and GLP, reports an LC50 of >1.5 mg/L air in rat, following 1-hour whole body inhalation exposure to vapour (Scientific Associates, 1977; rel 2).

The key acute dermal toxicity for dodecan-1-ol conducted according to a protocol similar to OECD Test Guideline 402 but not in compliance with GLP, reports and LD50 in the range of between 8000 and 12000 mg/kg bw/day in rabbits (Scientific Associates 1977f; rel 2).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Charles River (UK)

- Age at study initiation: 5 to 8 weeks

- Weight at study initiation: males 166-191g, females 131-158g

- Fasting period before study: overnight

- Housing: in groups of 5 by sex in solid floor polypropylene cages furnished with woodflakes.

- Diet: ad libitum

- Water: ad libitum

- Acclimation period: minimum 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 19 to 23

- Humidity (%): 49 to 55

- Air changes (per hr): ca. 15

- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

5M, 5F

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:The animals were observed for deaths and overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing on day 0 and on day 7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macrosopic abnormalities was recorded. No tissues were retained.

Preliminary study:

There were no deaths or clinical signs of toxicity. Based on this information a dose level of 2000 mg/kg bw was selected for the main study.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the study.

Gross pathology:

No abnormalities detected.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value of >2000 mg/kg bw is reported in a reliable study conducted according to the appropriate guideline. The study was compliant with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: other: contract laboratory protocol

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: COX-CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 216 to 253 grams

- Housing: Glass chamber for the duration of exposure to the test substance which after the animals were placed in individual wire-bottomed cages elevated above droppings.

- Diet: Purina laboratory Chow, pelletized (ad libitum)

- Water: ad libitum



IN-LIFE DATES: Not stated.

Route of administration:

other: mist

Type of inhalation exposure:

whole body

Vehicle:

other: atmosphere generated as a mist

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: DeVilbiss Nebulizer

- Exposure chamber volume: 57 litres

- Method of holding animals in test chamber: shared glass chamber

- Source and rate of air: six litres per minute


TEST ATMOSPHERE

- Brief description of analytical method used: non specified

- Samples taken from breathing zone: not specified



CLASS METHOD (if applicable)

- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

1 h

Concentrations:

71 mg/l

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The animals were observed for gross effects at regular intervals on the day of exposure and daily thereafter for fourteen days. All animals were weighed at the beginning and end of the test period.

Statistics:

No statistical analysis performed.

Preliminary study:

No preliminary study.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 71 mg/L air

Exp. duration:

1 h

Mortality:

All rats survived the 1 hour exposure and subsequent 14 day  observation period.

Clinical signs:

other: During exposure, all animals displayed hypoactivity and/or ataxia, salivation and gasping. Generalised weakness was also evident when the animals were removed from the chamber at the end of the exposure. At the 24 hour observation period, all animals show

Body weight:

Final bodyweight records of the animals at termination (14 days) showed gains within expected limits, in all animals.

Gross pathology:

Gross necropsy of the animals at fourteen days showed slight to moderate pulmonary (all animals) and adrenal (two animals) congestion; otherwise findings were unremarkable.

Other findings:

The lungs were affected in all rats.

Table 1: Concentrations, exposure conditions and number of evident toxicity per animals treated.

Nominal Conc. (mg/L)	Number with evident toxicity (#/total)
	Males	Females	Combined
71	0/5	0/5	0/10

 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation toxicity study with decan-1-ol, conducted prior to OECD Test Guideline and GLP, reported an LC50 of >71mg/L in rats, following 1-hour whole body inhalation exposure to the atmosphere generated as a mist.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: other: In house protocol

GLP compliance:

not specified

Test type:

fixed concentration procedure

Limit test:

no

Species:

rat

Strain:

other: COX-SD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS


- Weight at study initiation: 238-338g

- Housing: A 57 litre capacity glass chamber


ENVIRONMENTAL CONDITIONS

- Air changes (per hr): Air flow rate of 600 litres per hour



IN-LIFE DATES: Not stated

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: produced as a heated vapour

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION


- Exposure chamber volume: 57 litres

- Method of holding animals in test chamber: Animals were contained in a glass chamber.

- Source and rate of air: ALFOL 14 alcohol was introduced by passing an air flow over the test material as it was heated in a 60C at an ambient chambre concentration of approximately 1.5mg per litre of air at a flow rate of ten litres per minute for a period of one hour.


TEST ATMOSPHERE


- Samples taken from breathing zone: Prior to the actual test period, the test material was introduced into the chambre for six minutes, in order that the test atmospheric concentration could reach theoretical equilibrium.


VEHICLE

- Lot/batch no. (if required): 8714J



CLASS METHOD (if applicable)

- Rationale for the selection of the starting concentration: The 1.5mg/litre test concentration was chosen since the level does not exceed any to which man could be subjected to in any foreseeable use of the material.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

1 h

Concentrations:

1.5 mg/l

No. of animals per sex per dose:

5 female, 5 male

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Final body weight records of the ten animals at termination (14 days) showed weight gains within expected limits of that expected in all ten animals. The animals were observed frequently on the day of exposure and daily thereafter. Survivors were weighed and necropsied at the end of  the exposure period.

Statistics:

No statistical test was performed.

Key result

Sex:

male/female

Dose descriptor:

other: Inhalation

Effect level:

> 1.5 mg/L air

Exp. duration:

1 h

Mortality:

There were no mortalities during the exposure itself or in the 14 day observation period.

Clinical signs:

other: There were no clinical signs of toxicity present at any point of the study.

Body weight:

Body weight gain remained within expected limits for all ten animals.

Gross pathology:

Gross necropsy of the animals sacrificed at termination (14 days) showed no remarkable findings.

Other findings:

There were no other observations.

Table 1: Concentrations, exposure conditions and number of evident toxicity per animals treated

Nominal Conc. (mg/L)	MMAD µm	GSD	Number with evident toxicity (#/total)
			Males	Females	Combined
1.5mg/L			0 /5	0/5	0/10

 

Interpretation of results:

GHS criteria not met

Conclusions:

The rat 1 hour inhalational LC50 for tetradecan-1-ol is >1.5 mg/l. There were no signs of toxicity and findings at gross necropsy were unremarkable.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 500 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

application to abraded skin, use of occlusive coverage, limited information

Principles of method if other than guideline:

Method: other: contract laboratory protocol

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not specified
- Age at study initiation: not specified. Mention of 'young adults'
- Rationale for use of males: not specified
- Fasting period before study: No
- Weight at study initiation: 2.28-3.05 kg
- Housing: individual housing in metal cages which were elevated above the droppings. Prior to exposure, the animals were placed in a comfortable but immobilized position in a multiple animal holder
- Historical data: not specified
- Diet: Purina Rabbit Chow (ad libitum)
- Water: tap water (ad libitum)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified
- Humidity (%): Not specified
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): Not specified

IN-LIFE DATES: Not specified.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Intact and abraded skin of the trunk
- % coverage: Not specified
- Type of wrap if used: A plastic binder was slipped onto each animal and by means of a syringe, undiluted test material was introduced under the binder and spread evenly over the skin of the treatment site. The binder was then fastened tightly to keep the preparation in close contact with the skin for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Excess material was washed away and the area dried with absorbent paper towels. An estimate was made of the amount of unabsorbed material. After this, the animals were housed in their respective cages.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Total volume applied: maximum dose 11-12 ml/kg

VEHICLE
- Concentration (if solution): applied undiluted

Duration of exposure:

24 hours

Doses:

0.5, 1, 2, 4, 6, 8 and 12 g/kg

No. of animals per sex per dose:

2 males and females per dose (24 animals in total)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were weighted at the beginning and surviving animals were weighted at the end of the study period.

- Necropsy of survivors performed: yes

- Other examinations performed: The animals were observed for gross effects at regular intervals on the day of dosing and daily thereafter for 14 days.

Statistics:

No statistical analysis of the results was carried out.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 8 000 - <= 12 000 mg/kg bw

Based on:

test mat.

Mortality:

All deaths occurred between days 2 and 10 after administration. Number of deaths at each dose: Intact skin 0/2, 0/2, 2/2, 1/2, 1/2, abraded skin 0/2, 1/2, 0/2,0/2, 1/2, 1/2. Combined 0/4, 1/4, 2/4, 1/4, 2/4, 2/4.  The LD50 for combined abraded and intact skin was considered to be between 8 and 12 g/kg. The small group size and erratic dose response precluded separate estimation for intact and abraded skin.

Clinical signs:

other: At the end of the exposure period all animals showed slight to moderate erythema at the application site. In all survivors wrinkling and/or coriaceousness, hardeningand desquamation of the skin occurred and persisted in varying degrees until the end of th

Gross pathology:

Animals which died showed one or more of the following: depletion of visceral fatty tissue, moderate accumulation of clear fluid within the peritoneal cavity, moderate congestion of lungs  and kidneys, haemorrhaging and/or blanching with erosion of the gastric mucosa. Rabbits surviving to 14 days showed slight to moderate accumulation of clear viscous liquid within the peritoneal cavity and/or depletion of visceral fatty tissues. 9/16 rabbits showed no gross systemic changes.

Other findings:

- Potential target organs: gastric mucosa
- Other observations: More females than males succumbed to the effects of the test material.

Table 1:  Number of animals with abraded skin dead and the time range within which mortality occurred.

Dose (g/kg bw)       Mortality (# dead/ total) Males       Mortality (# dead/ total) Females       Mortality (# dead/ total) Combined       Time range of deaths (day)

0.5                            0/1                                                 0/1                                                 0/2                                                              NA

1.0                            0/1                                                 1/1                                                 1/2                                                               10

2.0                            0/1                                                 0/1                                                 0/2                                                               NA

4.0                            0/1                                                 0/1                                                 0/2                                                               NA

8.0                            0/1 or 1/1*                                     0/1 or 1/1*                                    1/2                                                                2

12.00                        0/1                                                 1/1                                                 1/2                                                                3

*1 Male or 1 Female (Not specified if 1 male or female with abraded/intact skin)

Table 2:  Number of animals with intact skin dead and the time range within which mortality occurred.

Dose (g/kg bw)       Mortality (# dead/ total) Males       Mortality (# dead/ total) Females       Mortality (# dead/ total) Combined       Time range of deaths (day)

0.5                            0/1                                                 0/1                                                        0/2                                                               NA

1.0                            0/1                                                 0/1                                                        0/2                                                               NA

2.0                            1/1                                                 1/1                                                        2/2                                                               9 and 13

4.0                            0/1                                                 0/1                                                        0/2                                                               NA

8.0                            0/1 or 1/1*                                     0/1 or 1/1*                                           1/2                                                                 7

12.00                        0/1                                                 1/1                                                        1/2                                                                 6

*1 Male or 1 Female (Not specified if 1 male or female with abraded/intact skin)

Table 3: Skin LD50 mortality [abraded and intact animals]

Dose (g/kg bw)       Mortality/No Animals       % Mortality

0.5                                   0/4 (0M, 0F)                     0

1.0                                   1/4 (0M, 1F)                     25

2.0                                   2/4 (1M, 1F)                     50

4.0                                   1/4 (0M, 1F)                     25

8.0                                   2/4 (1M, 1F)                     50

12.00                               2/4 (0M, 2F)                     50

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study, which predates GLP, conducted according to a protocol equivalent to OECD Test Guideline 402 (although guidelines not specified) with several deviations (application to abraded kin, use of occlusive coverage on immobilized animals) and some missing information (i.e., on test animals and environmental conditions), the rabbit dermal LD50 of dodecan-1-ol was concluded to be in the range of 8000 and 12000 mg/kg (24 occluded exposure). All test animals developed skin irritation at the application site persisting throughout the observation period. Clinical signs of toxicity were generalised weakness and unthriftiness. Haemorrhage and/or blanching with erosion of the gastric mucosa was reported in premature decedents but not in rabbits which survived to the end of the exposure period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

>= 8 000 mg/kg bw

Additional information

The key acute oral toxicity study for dodecan-1-ol, conducted according to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an LD50 value of >2000 mg/kg bw in rat (Safepharm Laboratory, 1996; rel 1). In the study, male and female rats were administered orally by gavage 2000 mg/kg bw of undiluted dodecan-1-ol. The animals were observed for deaths and overt signs of toxicity at 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing on day 0 and on day 7 and 14. At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. No mortality occurred during the 14-day observation period. No signs of systemic toxicity were noted during the study. All animals showed an expected body weight gain during the study. No abnormalities were detected at necropsy.

There are no acute inhalation toxicity data for dodecan-1-ol. Therefore data are read-across from decan-1-ol and tetradecan-1-ol.

The acute inhalation toxicity study with decan-1-ol, conducted prior to OECD Test Guideline and GLP, reports an LC50 of >71mg/L in rats, following 1-hour whole body inhalation exposure to the atmosphere generated as a mist (Scientific Associates 1977; rel 2). In the study, 5 rats were exposed to decan-1-ol atmosphere generated as a mist at a concentration of 71 mg/L by whole body inhalation exposure for 1 hour. The animals were observed for gross effects at regular intervals on the day of exposure and daily thereafter for 14 days. All animals were weighed at the beginning and end of the test period. At the end of the 14-day observation period, all the animals were subject to necropsy. All rats survived the 1-hour exposure and subsequent 14-day observation period. During exposure, all animals displayed hypoactivity and/or ataxia, salivation and gasping. Generalised weakness was also evident when the animals were removed from the chamber at the end of the exposure. At the 24-hour observation period, all animals showed reddened encrustation about the eyes, nose and roughened coat. Final bodyweight records of the animals at termination (14 days) showed gains within expected limits, in all animals. Gross necropsy of the animals at 14 days showed slight to moderate pulmonary (all animals) and adrenal (two animals) congestion. All other findings were unremarkable.

The acute inhalation toxicity study with tetradecan-1-ol, conducted prior to OECD Test Guideline and GLP, reports an LC50 of >1.5 mg/L air in rat (Scientific Associates, 1977; rel 2). In the study, 5 male and 5 female rats were exposed to tetradecan-1-ol vapour at a concentration of 1.5 mg/L by whole body inhalation exposure for 1 hour. The animals were observed frequently on the day of exposure and daily thereafter for 14 days. Survivors were weighed and necropsied at the end of the exposure period. There were no mortalities during the exposure itself or in the 14-day observation period. There were no clinical signs of toxicity present at any point of the study. Body weight gain remained within expected limits for all ten animals. Gross necropsy of the animals sacrificed at termination (14 days) showed no remarkable findings.

The key acute dermal toxicity for dodecan-1-ol conducted according to a protocol similar to the OECD Test Guideline 402 (although guidelines not specified) with some deviations and which predates GLP, reports an LD 50 in the range of between 8000 and 12000 mg/kg bw in rabbits (Scientific Associates 1977f; rel 2).  In the study, 500, 1000, 2000, 4000, 6000, 8000 and 12000 mg/kg bw undiluted dodecan-1-ol was introduced under a plastic binder by means of a syringe and spread evenly over the intact or abraded skin of 12 male and 12 female New Zealand albino rabbits for 24 hours. The binder was then fastened tightly to keep the preparation in close contact with the skin. The animals were observed for gross effects at regular intervals on the day of dosing and daily thereafter for 14 days. Body weights were recorded prior to dosing and on observation day 14. Following the observation period, all surviving animals were weighted, sacrificed, and necropsied.

At 24-hours following test application, all animals showed slight to moderate erythema of the skin at the treatment site. In all surviving animals, wrinkling and/or coriaceousness, hardening and desquamation of the skin occurred and persisted in all in varying degrees through termination. Generalised weakness preceded death in each animal. Signs of similar systemic effects, but to a lesser degree were observed in some of the surviving animals, however, eleven appeared systemically normal within 96 hours following exposure.  Gross necropsy of animal which succumbed showed one or more of the following abnormalities: depletion of visceral fatty tissue, moderate accumulation of clear fluid within the peritoneal cavity, moderate congestion of lungs and kidneys, haemorrhaging and/or blanching with erosion of the gastric mucosa. Rabbits surviving to 14 days showed slight to moderate losses of body weight (8/16), constant weight (2/16) and gains within expected limits in the 6 remaining animals;  slight to moderate accumulation of clear viscous liquid within the peritoneal cavity and/or depletion of visceral fatty tissues. 9/16 rabbits showed no gross systemic changes. The acute dermal LD50 of dodecan-1-ol when applied undiluted to the intact and abraded skin of young adult male and female New Zealand albino rabbits was found to be between 8000 and 12000 mg/kg bw.  

The supporting studies for all endpoints were in accordance with the key studies. The key studies were selected on the basis of most recent result and highest reliability available.

The supporting acute dermal toxicity study with dodecan-1-ol, which was conducted according to a protocol similar to OECD Test Guideline 402 (although guidelines not specified) with deviations, and which predates GLP, reports an LD50 in the range of 1500 and 2000 mg/kg bw/day in rabbits (Scientific Associates, 1975; rel 2). This older study was conducted according to a similar experimental procedure as the key study, but used fewer animals and fewer doses. Due to the deviations from the test guidelines, in particular, the application to the abraded skin, the use of an occlusive coverage on immobilised animals, the fact that gross pathological changes and gross necropsy are reported in general terms and no record is given for each animal, as well as the limited information given on environmental conditions, the study overall cannot be used for classification.

As the key and supporting study applied the test substance on intact and abraded skin and used an occlusive dressing on rabbits (which are sensitive animals, and not the preferred species), the key study was selected on the basis of the most recent result and highest reliability in terms of number of animals and doses tested, rather than on the worst-case value of the LD50. The LD50 range from the key acute dermal toxicity study being more statistically powerful, is also more in line with the dermal acute results from decan-1-ol (LD50 > 5000 in rats [Eurofins, 2009]) and tetradecan-1-ol (LD50 = 8000 mg/kg bw in rabbits and LD50 > 3320 mg/kg bw in rats [Scientific Associates 1977; Clark & Coombs 1978], the two closest linear substances of dodecan-1-ol in the category, and to a greater extent to the consistently low oral acute toxicity for the category as a whole. Indeed, in the key acute oral toxicity study for dodecan-1-ol, conducted according the now deleted OECD Test Guideline 401 and in compliance with GLP, an LD50 value of greater than 2000 mg/kg bw in rat was reported (SafePharm Laboratory, 1996; Rel 1). In general, considering the data for linear alcohols in the range octan-1-ol to docosan-1-ol and including unsaturated alcohols, the oral LD50 values range from > 5000 mg/kg to well over 10000 mg/kg, with most of values representing the maximum administered dose. Few, if any signs of toxicity were reported following oral administration of the linear alcohols ranging from C6 to C24 alcohols.

Since oral absorption is expected to be greater than dermal absorption at this chain length (C12), the dermal LD50 would not be expected to be lower than the oral LD50, therefore adding weight to selecting the higher LD50 as the key result and assuming the lower LD50 from the supporting study is an outlier due to the experimental limitations.

A full discussion of the Category and considerations of RAAF Assessment Entities can be found in the Human Health Alcohols C6-24 Category report (PFA, 2021).

Discussion of trends in the Category of C6-24 linear and essentially-linear aliphatic alcohols:

Acute toxicity tests of the linear and essentially linear alcohols do not indicate any potential hazard for acute, dermal or inhalation toxicity. The available data for the Category have been reviewed with the conclusion that the long chain alcohols are of a low order of acute oral and dermal toxicity, and the inhalation LC50 is expected to be greater than the substantially saturated vapour concentration (Veenstra G, Webb C et al., 2009). Tests on various substances included in this category are all supportive of these results and do not warrant classification for most of the acute toxicity endpoints under GHS criteria. The majority of the substances are therefore not classified for acute toxicity in accordance with Regulation (EC) No 1272/2008. The only exception to this is hexan-1-ol, which finds that the acute dermal data for the test substance are consistent with Acute dermal tox category 4 and Acute oral tox 4 H302/R22, in line with the Annex VI entry.

Justification for classification or non-classification

Based on the available data, dodecan-1-ol does not require classification for acute toxicity according to Regulation (EC) No 1272/2008.