Octadecan-1-ol

Endpoint summary

Description of key information

The key study for acute oral toxicity, conducted according to OECD TG 401, and in compliance with GLP, reports an LD50 value of >2000 mg/kg in rat (Safepharm Laboratories, 1991, rel 1). No information was available for the acute inhalation endpoint. However, further testing is not scientifically justified since high reliability data is in place for acute toxicity via the oral and dermal routes. Furthermore, weight of evidence across category suggests that the LC50 for inhalation is expected to be greater than the substantially saturated vapour concentration. The key acute dermal toxicity study was read-across from structurally analogous substance tetradecan-1-ol (CAS 112-72-1). The study was well documented and met generally accepted scientific principles, but was not compliant with GLP, reports an LD50 value of 8000 mg/kg in rabbit (Scientific Associates 1977; 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:

other: Sprague-Dawley CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Charles River (UK) Ltd., Margate, kent, UK.

- Age at study initiation: 5-8 weeks

- Weight at study initiation: 137-151g males, 124-135g females

- Fasting period before study: overnight

- Housing: The animals were housed in groupd of five by sex in solid floor polypropylene cages furnished with woodflakes.

- Diet: Rat and Mouse Expanded Diet No.1, ad libitum, Special Diets Services Ltd., Witham, Essex, UK

- Water: mains drinking water, ad libitum

- Acclimation period: minimum of five days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 19-22C

- Humidity (%): 39-60

- Air changes (per hr): ca. 15

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

Route of administration:

oral: gavage

Vehicle:

other: arachis oil

Details on oral exposure:

VEHICLE

- Concentration in vehicle: 10 mg/ml


MAXIMUM DOSE VOLUME APPLIED: 200 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 or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and for the remainder of the observation period. Individual bodyweights were recorded prior to dosing on Day 0 and on days 7 and 14.

- Necropsy of survivors performed: yes, the animals were killed by cervical dislocation

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The gross pathological examination consisted of external examination and opening of abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded.

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

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

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No other findings reported.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value of >2000 mg/kg was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.

Executive summary:

In an acute oral toxicity study, 2000 mg/kg of test material dissolved in arachis oil was administered to 5 male and 5 female rats. Body weight changes and clinical signs of toxicity were noted regularly during the 14 -day study period. Necropsy was performed at the end of the study.

There were no deaths during the 14 -day study period. No signs of systemic toxicity were observed. The expected gain in body weight was observed in all animals. No macroscopic abnormalities were observed at necropsy.

An LD 50 value of > 2000 mg/kg bw was reported. The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

no guideline followed

Principles of method if other than guideline:

Method: other: Contract laboratory protocol

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

no

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: The rabbits were individually housed in metal cages elevated above the droppings.

- Diet: Purina rabbit Chow (ad libitum)

- Water: Tap water (ad libitum)


IN-LIFE DATES: Not stated.

Type of coverage:

occlusive

Vehicle:

other: 50% w/w dilution tetradecanol in 1 % w/w gum tragacanth

Details on dermal exposure:

TEST SITE

- Area of exposure: The skin of the trunk which was clipped free of hair.

- Type of wrap if used: plastic binder


REMOVAL OF TEST SUBSTANCE

- Washing (if done): The binder was removed and the amount of unabsorbed substance estimated. The animals were then washed and the carefully blotted dry with absorbent hand towels.

- Time after start of exposure: The test compound was removed after 24 hours of exposure.


TEST MATERIAL


- Amount(s) applied (volume or weight with unit): The animals were distributed evenly as to sex in each of three dosage groups as follows: 2M+2F (1M+1F each intact and abraded) and dosed 2.0, 4.0 and 8.0 g/kg of the test substance.


- Concentration (if solution): A 50% w/w dilution of ALFOL 14 alcohol in 1% w/w gum tragacanth.



VEHICLE

- Amount(s) applied (volume or weight with unit): 1% w/w gum tragacanth.

Duration of exposure:

24 hours

Doses:

2, 4 and 8 g/kg

No. of animals per sex per dose:

2

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 fourteen days.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Body weights were recorded prior to dosing and on observation day 14.

Statistics:

No statistical analysis was carried out.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

8 000 mg/kg bw

Based on:

test mat.

Mortality:

100% of the animals with abraded skin died between 8 and 10 days of the exposure period. The animals with intact skin survived.

Clinical signs:

other: At twenty-four hours following test application, all animals showed slight to moderate erythema, desquamation, wrinkling and dryness of the skin at the treatment site. In all surviving animals, desquamation and wrinkling of the skin occurred and persisted

Gross pathology:

Gross necropsy of animals which succumbed showed depletion of visceral fatty tissue (one animal), moderate dermal irritation and desquamation at the treatment site (two animals). Gross necropsy of the animals which survived the 14 day observation period and were sacrificed, showed one animal with slight accumulation of clear viscous fluid within the peritoneal cavity and crazing over cortex of both kidneys. Eight animals showed no signs of gross systemic abnormalities.

Table 1: Number of animals dead within the 14 day observation period.

Dose (g/kg bw)	Mortality (# dead/total)			Time range of deaths (day)
	Male	Female	Combined
2.0	0/2	0/2	0/4	-
4.0	0/2	0/2	0/4	-
8.0	1/2	1/2	2/4 *	9 and 11

*thedead animals were from the group with skin prepared with abrasion.

 

Interpretation of results:

GHS criteria not met

Conclusions:

The rabbit dermal LD50 (24 hour occluded) for Alfol 14 was approx. 8000 mg/kg. All survivors showed skin irritation at the application site throughout the observation period. Signs of intoxication included weakness, emaciation and pallor. The result is read across from tetradecan-1-ol (CAS 112-72-1).

Executive summary:

In the acute dermal toxicity study, 2, 4 and 8 g/kg of test material was applied to the flanks of 2 male and 2 female rabbits per dose, kept in contact to the skin under occlusive dressing for 24 hours. The experiement was performed on intact and abrated skin. Body weight changes and clinical signs of toxicity were noted regularly. Necropsy was performed at the end of the 14 -day study period.

100% of the animals with abraded skin died between 8 and 10 days of the exposure period. The animals with intact skin survived. At twenty-four hours following test application, all animals showed slight to moderate erythema, desquamation, wrinkling and dryness of the skin at the treatment site. In all surviving animals, desquamation and wrinkling of the skin occurred and persisted in varying degrees throughout the 14 -day study period. At the highest dosage level (8 g/kg body weight, two of the surviving animals showed signs of weakness, emaciation and pallor; however all appeared systematically normal within 96 hours following exposure. Final body weight records of the surviving animals at termination, showed a slight loss in one animal, a constant weight in one animal and gains within expected limits in the eight remaining animals. At necropsy, there was one animal with slight accumulation of clear viscous fluid within the peritoneal cavity and crazing over cortex of both kidneys. Eight animals showed no signs of gross systemic abnormalities.

An LD50 value of 8000 mg/kg bw was reported. The study was well documented and meets generally accepted scientific principles, but was not conducted in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

8 000 mg/kg bw

Additional information

The acute oral supporting studies are in accordance with the key findings, reporting LD50 values of >5000mg/kg (Henkel 1981; rel 1) and >7960 mg/kg (Scientific Associates 1965; rel2) in rat. The most recent and high reliability study was chosen as key study for the acute oral toxicity endpoint and reports an LD50 value of > 2000 mg/kg bw. The data for inhalation toxicity was waived based on weight of evidence across category and the acute dermal read across from tetradecan-1-ol (CAS 112-72-1) which was the most structurally analogous substance available. The key acute dermal study reports an LD50 value of 8000 mg/kg bw.

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. 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, octadecan-1 -ol does not require classification for acute toxicity according to Regulation (EC) No 1272/2008.