Octan-1-ol

Endpoint summary

Description of key information

In the key acute oral toxicity study for octan-1-ol, conducted according to an appropriate OECD Test Guideline 401 but full details were not available, and in compliance with GLP, an LD50 value of >5000 mg/kg bw was reported when applied as an aqueous solution (Henkel, 1981; rel 2).

In the key acute dermal toxicity study for octan-1-ol, which was well-documented and meets generally accepted scientific principles, although conducted prior to GLP, an LD50 value of 2000-4000 mg/kg bw was reported (Scientific Associates 1976; 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Winkelmann, Hanover, Germany

- Weight at study initiation: mean body weight males, 137, females 127

- Fasting period before study: fasted, time not specified

Route of administration:

oral: gavage

Vehicle:

other: as an aqueous suspension

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 25% aqueous suspension at a constant volume of 20 ml/kg.

Doses:

5 g/kg single dose level

No. of animals per sex per dose:

5M, 5F

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:  Body weights were recorded prior to dosing and at  24 hours, 1 week and 2 weeks after dosing. 

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Clinical signs were observed particularly during the first 24 hours after dosing.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the course of the study.

Clinical signs:

other: During the first 24 hours all test animals showed some decrease in actvity and piloerection.  No adverse effects were observed during the 14 day observation period.

Gross pathology:

The were no abnormal findings.

Other findings:

No potential target organs identified, no sex xpecific differences detected.

Interpretation of results:

GHS criteria not met

Conclusions:

The rat oral LD50 for Lorol 8 was >5g/kg when applied as an aqueous suspension. Clinical signs of intoxication were confined to slight sedation and piloerection during the first 24 hours following dosing. There was no remarkable gross pathology at necrospy and no indication of specific target organ toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 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:

1976

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:

other: LD50

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: 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.

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.

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.

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

In the key acute oral toxicity study for octan-1-ol, conducted according to an appropriate OECD Test Guideline 401 but full details were not available, and in compliance with GLP, an LD50 value of >5000 mg/kg bw was reported when applied as an aqueous solution (Henkel 1981; rel 2). In the study, octan-1-ol was administered by oral gavage to 5 male and 5 female rats as an aqueous solution at dose level of 5000 mg/kg bw. Clinical signs and body weights were recorded on a regular basis for 14 days. At the end of the 14-day observation period, the animals were sacrificed and subject to gross pathology. No deaths occurred during the course of the study. During the first 24 hours post-test item administration all test animals showed some decrease in activity and piloerection. No adverse effects were observed during the 14 day observation period. No changes in body weight gain were noted. There were no abnormalities noted at gross necropsy.

The reliability 2 oral supporting study by Scientific Associates (1965) found the LD50 to be 18240 mg/kg in rat. The remaining supporting studies are reliability 4, and in accordance with the key information.

In the key acute dermal toxicity study for for octan-1-ol, which was well-documented and meets generally accepted scientific principles although conducted prior to GLP, an LD50 value of 2000-4000 mg/kg bw was reported (Scientific Associates 1976; rel 2). In the study, undiluted octan-1-ol was applied onto the intact and abraded skin of male and female rabbits for 24 hours under occlusive dressing at doses of 1000, 2000 and 4000 mg/kg bw. The animals were observed for gross effects at regular intervals on the day of dosing and daily thereafter for 14 days. Mortality, clinical signs 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 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 at 1000, 2000 and 4000 mg/kg bw, respectively. A visual assessment of test site suggested that >75% of  the dose was observed at each dose level. At the end of the exposure period all animals showed slight to severe erythema and oedema particularly 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. These signs persisted and/or intensified in animals which eventually died. Final body weights of surviving animals showed moderate to severe loss in 2 animals, constant weight in 3 animals, and slight to moderate  gain in 3 animals. 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). 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 haematuria 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.

Overall, 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 pathological finding was erosion of the gastric mucosa. However, the test material is considered to be not toxic according to current guideline.

A supporting acute dermal toxicity study is available that reports an LD50 value of > 5000 mg/kg bw.

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, 2016).

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 toxicity category 4 and Acute oral toxicity 4 H302/R22, in line with the Annex VI entry.

Justification for classification or non-classification

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