Dodecan-1-ol

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Dodecan-1-ol

EC Number:

203-982-0

EC Name:

Dodecan-1-ol

Cas Number:

112-53-8

Molecular formula:

C12H26O

IUPAC Name:

dodecan-1-ol

Test animals

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.

Administration / exposure

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.

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.