Octan-1-ol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

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:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: other: contract laboratory protocol

GLP compliance:

not specified

Test type:

other: LD50

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Octan-1-ol

EC Number:

203-917-6

EC Name:

Octan-1-ol

Cas Number:

111-87-5

Molecular formula:

C8H18O

IUPAC Name:

octan-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

- Weight at study initiation: 2.3 to 2.9 kg

- Housing: During the exposure the animals were placed in a multiple animal holder in an immobilized position. After the 24 hour exposure period the animals were placed in their respective metal cages elevated above the droppings for the duration of the 14 day observation period.

- Diet: Purina Rabbit Chow (ad libitum)

- Water: tap water (ad libitum)


IN-LIFE DATES: No data available.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: undiluted test substance

Details on dermal exposure:

TEST SITE

- Area of exposure: Skin of the trunk. One half of the animals in each group were prepared by making epidermal abrasions every two or three centimeters longitudinally over the area of exposure.

- Type of wrap if used: plastic binder.


REMOVAL OF TEST SUBSTANCE

- Washing (if done): At the end of the period of exposure the plastic binders were removed, and the remaining test compound washed from the animals' bodies. The animals were then blotted dry with absorbent paper hand towels.

- Time after start of exposure: 24 hours.


TEST MATERIAL

- Amount(s) applied (volume or weight with unit): maximum dose 3-4 ml/kg

- Concentration (if solution): Doses 1, 2 and 4g/kg of body weight.

- Constant volume or concentration used: Not specified.



VEHICLE

- Applied undiluted

Duration of exposure:

24 hours.

Doses:

1, 2 and 4 g/kg

No. of animals per sex per dose:

For 1g/kg dose: 2M, 2F, for 2g/kg dose: 4M, 4F, for 4g/kg dose 2M, 2F.

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 gross effects at regular intervals on the day of dosing and daily thereafter for 14 days.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Mortality, clinical signs of systemic toxicity and skin reactions at the application site were recorded on the day of dosing and  throughout the 14 day observation period. Body weights were recorded  prior to dosing and on observation day 14. All decedents and survivors were subject to gross necropsy.

Statistics:

No statistical analysis was carried out in this study.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 - 4 000 mg/kg bw

Mortality:

Time of death: All deaths occurred within 4 days of exposure.  Number of deaths at each dose: Intact skin 0/2, 1/4 and 2/2, abraded skin 0/2, 3/4 and 2/2. LD50(s): Intact skin: 2-4 g/kg; Abraded skin: 1-2 g/kg; combined intact and abraded 2 g/kg. A visual assessment of test site suggested that >75% of  the dose was observed at each dose level.

Clinical signs:

other: At the end of the exposure period all animals showed slight to severe erythema and oedema particulary of the ventral skin and  particularly in animals with abraded skin. In all survivors wrinkling and coreaceousness gradually developed forming an inelast

Gross pathology:

In animals which succumbed there was severe skin damage with maceration and erosion of the ventral skin and  musculature. Blanching and multiple focal haemorrhages of the gastric mucosa, friability of the liver, moderate heamaturia and a slight  accumulation of  amber, watery peritoneal fluid were observed internally. Rabbits surviving to 14 days showed moderate to marked desquamation, severe erosion and multiple focal haemorrhages of the gastric mucosa  and slight accumulation of clear or amber viscous fluid in the peritoneal cavity.

Other findings:

The experimental data was reported in combined form with no mention of sex differences.

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)			Time range of deaths (day)
	Male	Female	Combined
1.00			0/2
2.00			3/4	2 and 3
4.00			2/2	1 and 2

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

Dose (g/kg bw)	Mortality (# dead/total)			Time range of deaths (day)
	Male	Female	Combined
1.00			0/2
2.00			1/4	4
4.00			2/2	2 and 4

 

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

The substance does not classify for acute dermal toxicity according to Regulation (EC) No 1272/2008.

Conclusions:

The rabbit dermal LD50 for Alfol 8 following 24 hour occlusive exposure was 2000-4000 mg/kg. There was significant evidence of skin irritation at the application site persisting in some animals throughout the observation period. Clinical signs were indicative of a general toxic effect coupled with anorexia. The most common gross pathogical finding was erosion of the gastric mucosa. Not classified according to EU criteria.

Executive summary:

In the acute dermal toxicity study 1, 2 and 4 g/kg (1000, 2000, 4000 mg/kg) of undiluted test material were applied onto intact and abrated rabbit skin kept in contact to the skin for 24 hours under occlusive dressing. The animals were observed for gross effects at regular intervals on the day of dosing and daily thereafter for 14 days.

Mortality, clinical signs of systemic toxicity and skin reactions at the application site were recorded on the day of dosing and throughout the 14 day observation period. Body weights were recorded prior to dosing and on observation day 14. All decedents and survivors were subject to gross necropsy. All deaths occurred within 4 days post-exposure. At the end of the exposure period all animals showed slight to severe erythema and oedema particulary of the ventral skin and particularly in animals with abraded skin. In all survivors wrinkling and coreaceousness gradually developed forming an inelastic sheath around the trunk of the animal. The healing process continued throughout the 14 day observation period. Generalised weakness and inactivity was evident in most animals following exposure. Survivors appeared normal at 72 hours post exposure.  Final body weight of surviving animals at termination (14 days) showed moderate to severe loss (2 animals), a constant weight (3 animals) and slight to moderate gain (3 animals).

n animals which succumbed there was severe skin damage with maceration and erosion of the ventral skin and  musculature. Blanching and multiple focal haemorrhages of the gastric mucosa, friability of the liver, moderate heamaturia and a slight accumulation of amber, watery peritoneal fluid were observed internally. Rabbits surviving to 14 days showed moderate to marked desquamation, severe erosion and multiple focal haemorrhages of the gastric mucosa and slight accumulation of clear or amber viscous fluid in the peritoneal cavity.

An LD 50 value of > 2000 -4000 mg/kg bw was concluded. The study was well documented and meets generally accepted scientific principles, but was conducted prior to international GLP guidelines.