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Administrative data

Description of key information

A reliability 2 acute oral key study reports an LD50 value of 3210 mg/kg in rat (Scientific Associates Inc 1965). For acute inhalation, an LC50 value of >21 mg/L air (mist) is given in a reliability 2 key study in rat (Scientific Associates Inc 1977). Finally, the acute dermal key study in rabbit reports a LD50 value of 1500-2000 mg/kg bw, which is a combined value for intact and abraded skin.

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:
other: The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
other: LD50
Limit test:
no
Species:
rat
Strain:
other: Holtzman albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 200-265g

- Fasting period before study: Over night

- Housing: Group housing (5 of each sex per cage), in metal cages provided with white pine and cheddar shavings.

- Diet: Purina Laboratory Chow, ad libitum.

- Water: ad libitum




Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Exploratory doses were administered to 8 rats to estimate the order of toxicity of the test compound. Based on the preliminary estimation, groups of 10 rats (5M, 5F) were administered the test compound at graded dosage levels designed to blanket the toxicity range.
Doses:
1.17, 1.65, 2.33, 3.28, 4.64 and 6.55 gm/kg
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

- Frequency of observations and weighing: 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: Gross necropsies were performed on all  survivors and any animals which died during the observation period. Body weights of survivors were recorded prior to sacrifice.
Statistics:
Confidence Interval 2.85 ml (2.35 gm) to 5.34ml (4.39gm)/kg body weight. Slope function 1.88, with confidence interval of 1.26 to 2.80.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 210 mg/kg bw
Mortality:
All deaths occurred within 24 hours of dosing. See table. 

.
Clinical signs:
Animals at all dose levels exhibited weakness and ataxia. They became comatose and breathing was laboured while comatose. 
Animals  which survived appeared normal within 24 hours other than top dose animals (6.55 g/kg) where the rats appeared unwell up to 48 hours 
after dosing. 
Body weight:
Weight gain amongst survivors was within normal limits.
Gross pathology:
Necropsy of animals which died showed congestion of  the lungs and adrenals in most animals. In some cases gastric 
congestion  was also observed. There were no remarkable gross findings in animals sacrificed at the end of the observation period.
Other findings:
- Organ weights: Not recorded

- Histopathology: Not available

- Potential target organs: No conclusion drawn

- Other observations: No sex specific differences were reported, mortality represented as a combined value so no independent assesment can be made.

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

 

Dose
ml (and gm.) kg./body weight

Mortality (# dead/total)

Time of death (day)

Male

Female

Combined

1.42 (1.17)

 

 

0/10 

 

2.00 (1.65)

 

 

 1/10

 1

2.83 (2.33)

 

 

4/10

 1

3.99 (3.28)

 

 410

 1

5.64 (4.64)

 

 

8/10

1

7.96 (6.55)

 

 

8/10

1

 

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value of 3.21 g/kg was determined in a reliable study conducted according to an appropriate test protocol. Not conducted according to GLP.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 210 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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 available
Principles of method if other than guideline:
Only one dose level, short exposure period, no indication of droplet size.
GLP compliance:
not specified
Test type:
other:
Limit test:
no
Species:
rat
Strain:
other: T23-48:COX-SD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 245-356g

- Housing: 57 litre capacity glass chamber

- Diet: Purina laboratoy chow (ad libitum)

- Water: yes (ad libitum)


IN-LIFE DATES: Not specified.
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: Free to move in the glass chamber

- Source and rate of air: Delivery flow concentration of approximately 21 mg per litre of air, at a flow rate of six litres per minute.



TEST ATMOSPHERE

- Brief description of analytical method used: Prior to the actual exposure period, the test material was introduced into the chambre for ten minutes in order to make sure the test atmospheric concetration could reach theoretical equilibrium.

- Samples taken from breathing zone: no


TEST ATMOSPHERE (if not tabulated)

- Particle size distribution: Droplet size not reported
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
1 h
Concentrations:
21 mg/l
No. of animals per sex per dose:
5 male, 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed frequently for gross effects during the exposure and daily thereafter for 14 days.

- Necropsy of survivors performed: yes

Statistics:
No statistical analysis was carried out on the test results.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 21 mg/L air
Exp. duration:
1 h
Mortality:
All animals survived the 14 day observation period.
Clinical signs:
other: During exposure all animals showed hypoactivity and/or ataxia, lethargy and prostration. However within 2 hours of removal from the exposure chamber the animals all appeared and continued to appear normal throughout the observation period.
Body weight:
Final bodyweights showed a  slight weight loss in one animal however the others all exhibited weight gains within expected limits.
Gross pathology:
Gross necropsy revealed moderate pulmonary, adrenal and hepatic congestion in one animal only. The findings in the remaining 9 test animals were unremarkable.
Other findings:
No potential target organs were identified.
Interpretation of results:
GHS criteria not met
Conclusions:
The rat inhalational LC50 following a 1 hour exposure to a mist of Alfol 6 was >21 mg/l. Since the test atmospheric concentration would in all probablility exceed that to be encountered by humans when the substance is used, hexan-1-ol was found not to be a toxic substance.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
21 mg/m³

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)
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
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
- test material was applied to intact and abraded skin.
Duration of exposure:
24 hours
Doses:
0.5, 1, 1.5 and 2 g/kg
No. of animals per sex per dose:
2M, 2F
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed for clinical signs of intoxication several time during the day of dosing and daily thereafter throughout  the 14 day observation period.  The animals were weighed at sacrifice.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 500 - < 2 000 mg/kg bw
Mortality:
- Time of death: Within 48 hours of dosing.
- Number of deaths at each dose: 0/4, 1F/4, 1M/4, 4/4.
Clinical signs:
Prior to death generalised weakness and/or unthriftiness, diarrhoea, hypothermia, pallor, loss of corneal and palepebral reflexes, hunched position, flaccidity, slow shallow repsiration and coma. Similar signs of intoxication but less marked were observed in survivors. All survivors appeared systemically normal within 96 hours of dosing. 
Body weight:
Among survivors there was weight loss in 3 rabbits, one rabbit maintained a constant weight, while the remaining survivors showed weight gains within expected limits.
Gross pathology:
Premature decedents showed at gross necropsy, in addition to dermal irritation, severe haemorrhaging and/or bloody,  gelatinous infiltration of the subcutis, depletion of fatty tissue, slight accumulation of clear fluid within the peritoneal cavity, moderate congestion of liver and kidneys and severe haemorrhaging and/or blanching  of the gastric mucosa. Amongst survivors (10), other than residual skin damage, gross necropsy findings were unremarkable in 7 rabbits. In the remaining 3 rabbits there was a slight to moderate accumulation of clear viscous liquid in the peritoneal cavity and/or a dpeletion of visceral fat and mottling or stippling of the renal cortex.

Rabbit dermal LD50 (24 hour occlusive exposure) 1.5 - 2 g/kg. This is a combined value for intact and abraded skin and males/females. 

At 24 hours all animals showed slight to moderate erythema especially of the ventral region. Survivors all showed wrinkling 

and/or coriaceousness, hardening and desquamation of the skin which persisted throughout the observation period.



Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The rabbit dermal 24 hour occlusive LD50 (combined applications to intact and abraded skin) is 1500-2000 mg/kg.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 500 mg/kg bw

Additional information

The available key and supporting data on the acute oral toxicity of hexan-1-ol (CAS 111-27-3) comprises the following: a reliability 2 key study by Scientific Associates Inc. (1965) reports an LD50 value of 3210 mg/kg in rat. Clinical signs included weakness and ataxia, all surviving animals appearing normal within 48 hours of dosing. Necropsy of decedents revealed congestion of the lungs and adrenals, as well as gastric congestion in some cases. No remarkable gross findings were observed in animals sacrificed at the end of the observation period.

 

This result is supported by reliability 2 study from Scientific Associates Inc. (1977) which reports the LD50 value of 4420 mg/kg in rat, with clinical signs of hypoactivity, diarrhoea and ataxia, gastric mucosa identified as a potential target organ.

 

Additional reliability 4 supporting studies report LD50 values of 4000 mg/kg in mouse (Bevan, 2001), 4590 mg/kg in rat (IUCLID 2000), 4870 mg/kg in rat (Bevan, 2001), 3131-3344 mg/kg (species unclear) (IUCLID 2000) and 1950 mg/kg in mouse (IUCLID 2000). Several LD50 values for rat are also reported in IUCLID 2000 ascribed to either Henkel or the Dangerous Properties of Industrial Materials Report between 4000 and 4900 mg/kg.

 

Further investigation of some data listed in IUCLID 2000 and Sax 'Dangerous Properties of Industrial Materials' has led to a reported LD50 in rat of 720 mg/kg bw. While this is an old study (1969) with some methodological and reporting deficiencies, on balance it can be considered reliability 2 data and should be taken into account.

The key acute inhalation study (Scientific Associates Inc., 1977) in rat reports an LC50 value of >21mg/L air with unremarkable necropsy findings in the majority of the animals. The study is equivalent to current guideline. Two supporting studies of reliability 4 are also provided, with an 8 hour LC50 which was found to be greater than a substantially saturated vapour concentration (Bevan, 2001) and an LC50 >1060ppm (Opdyke, 1975) with very little experimental detail available. The key study for hexan-1-ol acute dermal toxicity (reliability 2) from Scientific Associates Inc. (1977) reports a rabbit LD50 value of 1500-2000 mg/kg. Clinical signs prior to death included (but were not limited to) weakness, diarrhoea, slow shallow respiration and coma. Similar, but less marked signs of intoxication were observed in survivors who appeared normal within 96 hours of dosing. Premature decedents showed severe haemorrhaging and/or bloody, gelatinous infiltration of the subcutis, depletion of fatty tissue, accumulation of fluid within peritoneal cavity and moderate congestion of liver and severe haemorrhaging and/or blanching of the gastric mucosa. In the survivors, 7 of the animals showed no remarkable findings at necropsy, but the remaining 3 had a slight to moderate accumulation of clear viscous fluid in the peritoneal cavity and/or depletion of visceral fat and mottling or strippling of the renal cortex.

A supporting, reliability 2 study by Scientific Associates Inc. (1980) reported a rabbit dermal LD50 value of 2330 mg/kg with clinical signs and necropsy findings similar to the key study. The remaining reliability 4 data reports LD50 values of 2530 mg/kg and >5000 mg/kg (IUCLID 2000). Other LD50 values reported in IUCLID 2000 were ascribed to either Henkel or the Dangerous Properties of Industrial Materials were within the range of 2530-2500 mg/kg.

As shown above, the key dermal result falls within the classifiable range and would be consistent with CLP classification. This appears to be the most sensitive result from a consistent range ca. 1500-2600 mg/kg. The consistency of findings between the key result and others available suggests the findings of the 1977 study were not aberrant.

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 EC regulation 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

Hexan-1-ol is classified as Acute oral tox Category 4, H301, in Annex VI of Regulation (EC) No 1272/2008. The available data indicate that classification as Acute dermal tox Category 4, H312 in accordance with Regulation (EC) No 1272/2008 is also appropriate.