Alcohols, C16-18

Endpoint summary

Description of key information

- Acute oral toxicity: The acute oral LD50 in male/female rats is >10000 mg/kg bw . No significant gross abnormalities were seen at autopsy. )). This show that Alcohols, C16-18  is practically nontoxic for acute oral toxicity.  Alcohols, C16-18 was not classified according to EU or GHS criteria.
 -Acute Dermal Toxicity: The rabbit dermal LD50 (24 hour occluded) for Alcohols, C16-18 was  >8000 mg/kg applied as a 50% solution in peanut oil. There  were no deaths or reports of toxicity. This show that Alcohols, C16-18 is not  toxic for acute Dermal toxicity . Alcohols, C16-18 was not classified according to EU or GHS criteria
 
-Acute inhalation toxicity : Inhalation of vapours of Alcohols, C16-18 at levels up to the saturated vapour pressure is unlikely to be associated with significant toxicity. The LC50 values exceeded the maximum achievable vapour concentrations and showed no evidence of toxicity after a single exposure for 6 hours . Results indicate that  Alcohols, C16-18 is not toxic for acute inhalation toxicity. Alcohols, C16-18 was not classified according to EU or GHS criteria.

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:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Method: other: in house protocol

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: Rat (Sprague-Dawley)
- Source: Not reported
- Weight at study initiation: 200-245 g
- Group size: 5 (a group of 5 is used at each dose level but it is not clear how the sexes were distributed among the dose levels as the report states both were used). The rats were fasted.
- Controls: none
Sex: male/female
No. of Animals: 20

Route of administration:

oral: gavage

Vehicle:

other: 20% aqueous suspension prepared in 0.5% gum tragacanth

Details on oral exposure:

Vehicle: other: 20% aqueous suspension prepared in 0.5% gum tragacanth
Doses: 2, 4, 5 and 10 g/kg,

Doses:

Doses: 2, 4, 5 and 10 g/kg,

No. of animals per sex per dose:

Group size: 5 (a group of 5 is used at each dose level but it is not clear how the sexes were distributed among the dose levels as the report states both were used).

Control animals:

no

Details on study design:

ADMINISTRATION: Gavage
- Doses: 2, 4, 5 and 10 g/kg (based on range finding test)
- Doses per time period: single
- Volume administered or concentration: 20% aqueous suspensioin in 0.5% gum tragacanth.
- Post dose observation period: 14 days

EXAMINATIONS: Mortality was recorded.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died.

Clinical signs:

other: Not reported.

Gross pathology:

No significant gross abnormalities were seen at autopsy.

Other findings:

NECROPSY FINDINGS: Not carried out.
POTENTIAL TARGET ORGANS: None identified.
SEX-SPECIFIC DIFFERENCES: Combined test group.

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 in male/female rats is >10000 mg/kg bw . No significant gross abnormalities were seen at autopsy.
The rat oral LD50 for Alcohols, C16-18 was >10000 mg/kg bw.

Executive summary:

The rat oral LD50 for Alcohols, C16-18 was >10000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 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

Justification for type of information:

Alcohols, C16-18 is a member and is from Long Chain Alcohols (C6-22 primary aliphatic alcohols) category.
The Long Chain Alcohols (C6-22 primary aliphatic alcohols) category is considered suitable as a source of data for Alcohols, C16-18.
Considered valid for read-across for purposes of classification.
No further vertebrate testing can be justified.

Long Chain Alcohols (C6-22 primary aliphatic alcohols) category covers a family of 30 primary aliphatic alcohols within a carbon chain length range of C6-C22. Commercial products generally include several aliphatic alcohol components, with a range of carbon chain lengths present. The family consists of alcohols with varying compositions and structures. Composition depends on the route to manufacture and the related feedstocks. Most of the alcohols have linear carbon chains but certain manufacturing processes create branched structures. Data are also available for eleven other similar substances, which support the category. Non-sponsored alcohols may not be HPV or may not be produced by members of the consortium, but have structures similar to sponsored linear alcohols.

Key points are that the members share:
• The same structural features
• Similar metabolic pathways
• Common mode of ecotoxicological action
• Common levels and mode of human health related effects.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

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:

acute toxic class method

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.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 21 mg/L air

Based on:

test mat.

Exp. duration:

1 h

Remarks on result:

other: To convert mg/l into mg/m³ 1 mg/m³=mg/l x 1000, 21mg/lx1000=21000 mg/m³

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 025 ppm

Based on:

test mat.

Exp. duration:

1 h

Remarks on result:

other: To convert mg/m3 into ppm at 25°C and 760 mm Hg (101.32 kPa) ppm = mg/m3 x (24.45/molecular weight) 21000 x (24.45/102.18)=5025 ppm

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 21 000 mg/m³ air

Based on:

test mat.

Exp. duration:

1 h

Remarks on result:

other: To convert ppm into mg/m3 at 25°C and 760 mm Hg (101.32 kPa) mg/m3 =ppm x molecular weight /24.45. mg/m3  =5025x 102.18/24.45=21000 mg/m3                          

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

Other findings:

No potential target organs were identified.

To convert mg/l into mg/m³

1 mg/m³=mg/l x 1000,

21mg/lx1000=21000 mg/m³

To convert mg/m3 into ppm at 25°C and 760 mm Hg (101.32 kPa)

ppm = mg/m³ x 24.45

molecular weight

21000 x (24.45/102.18)=5025 ppm

To convert ppm into mg/m3 at 25°C and 760 mm Hg (101.32 kPa)

mg/m³ =ppm x molecular weight

                           24.45

mg/m³  =5025x 102.18 =21000

                           24.45

Interpretation of results:

other: practically nontoxic

Remarks:

Criteria used for interpretation of results: other: Federal Hazardous Substances Act

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, Alfol 6 Alcohol was found not to be a toxic substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

21 000 mg/m³ air

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

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: screening test
One rabbit was exposed at each of 5 dose levels ranging from 1 to 10 g/kg. The treated area was covered with a plastic shield for an exposure period of 24 hours. The animals were then observed for 14 days.

GLP compliance:

not specified

Test type:

other: screening test

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: Rabbit (New Zealand White)
- Source: Not reported.
- Weight at study initiation: 2.3-3 kg
- Group size: 5 (sex unspecified

Type of coverage:

occlusive

Vehicle:

other: undiluted (heated to melting point)

Details on dermal exposure:

ADMINISTRATION: 24 hour occluded exposure
- Area covered: trunk of animal
- Occlusion: plastic sleeve
- Vehicle: undiluted (heated to melting point)
- Doses: 1, 2.5, 5, 7.5 and 10 g/kg
- Removal of test substance: not reported

EXAMINATIONS: Mortality, behaviour and weight gain were observed over the 14 day observation period.

Duration of exposure:

24 hour occluded exposure

Doses:

1, 2.5, 5, 7.5 and 10 g/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

EXAMINATIONS: Mortality, behaviour and weight gain were observed over the 14 day observation period.
One rabbit was exposed at each of 5 dose levels ranging from 1 to 10 g/kg. The treated area was covered with a plastic shield for an exposure period of 24 hours. The animals were then observed for 14 days.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the exposure and observation period.

Clinical signs:

other: None reported.

Gross pathology:

Not carried out.

Other findings:

POTENTIAL TARGET ORGANS: None identified
SEX-SPECIFIC DIFFERENCES: Sex not specified.

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The rabbit dermal LD50 (24 hour occluded) for Alcohols, C16-18 was >10000 mg/kg . There were no deaths or reports of toxicity.

Executive summary:

All 5 animals survived. The LD50 was found to be greater than 10,000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Additional information

Acute oral toxicity

Alcohols, C16-18 is from the category of Long Chain aliphatic Alcohols within a carbon chain length range of C6-C22. Considering the data for linear alcohols in the range 1-octanol to 1-docosanol and including unsaturated alcohols, the oral LD50values range from > 5000 mg/kg to well over 10,000 mg/kg, with most of values representing the maximum administered dose.

ClinicalSigns. Few, if any signs of toxicity were reported following oral administration of the linear alcohols ranging from C6 to C22 alcohols. At doses approaching acute lethality loss of appetite, lethargy and diarrhoea was reported for most members of the linear alcohols. Animals surviving a large oral dose showed no evidence of any delayed or irreversible effects following acute administration of any of these alcohols. In decedents irritation of the gastro-intestinal tract and typical agonal changes were observed, however no substance specific observations could be recognised for any of the materials of this sub-category. There are no observations reported to suggest a potential for CNS depression following administration of a single oral dose of a linear alcohol within this category.

Conclusion:The category of the long chained aliphatic alcohols (linear and essentially linear) is of a low order of acute toxicity upon oral administration.Alcohols, C16-18 was not classified according to EU or GHS criteria.

 

Acute inhalation toxicity

Alcohols, C16-18 is from the category of Long Chain aliphatic Alcohols within a carbon chain length range of C6-C22.The available data cover the lower (1-hexanol and 1-octanol), intermediate (1-decanol, 1-dodecanol) and higher (1-tetradecanol, C16-18alcohols) chain-lengths of the linear alcohols subcategory.

The volatility of the category of aliphatic alcohols as a whole is low. Saturated vapour pressures for the higher chain alcohols are extremely low; for example the calculated concentration of a saturated atmosphere of 1-dodecanol and 1-octadecanol at ambient conditions is in the order of 10-2and 10-5mg/L, respectively. Most experimental studies used the maximum achievable vapour concentrations or aerosols for the assessment of the acute lethal concentration. For all substances tested the LC50values exceeded the maximum achievable vapour concentrations. Even the more volatile members of this category (e.g. 1-hexanol, C6-12 essentially linear alcohols [Types B and C], 1-heptanol and 1-undecanol) showed no evidence of toxicity after a single exposure for 1 – 6 hours

None of the acute inhalation studies provided any evidence of a potential for CNS depression for the category of aliphatic alcohols. This conclusion is further supported by data in mice indicating that inhalation of high concentrations (up toca. 10,000 ppm) of 1-heptanol for short periods of time did not induce anaesthesia.

Conclusion: Inhalation of vapours of long chained alcohols in the range C6-C22 at levels up to the saturated vapour pressure is unlikely to be associated with significant toxicity.Alcohols, C16-18 was not classified according to EU or GHS criteria.

 

Acute Dermal Toxicity

Alcohols, C16-18 is from the category of Long Chain aliphatic Alcoholswithin a carbon chain length range of C6-C22.

For the linear alcohols in the range, C6 - C10 most of the reported LD50values in rabbits are in the range 2000 - 4000 mg/kg. For the alcohols C12and higher the acute dermal LD50values were 8000 mg/kg or higher. Although some incidental LD50values below 2000 mg/kg were reported, these values generally represented the maximum dose tested. Substances with a chain length beyond C18 have not been tested but on the basis of the consistent low acute dermal toxicity for alcohols with a chain-length of C16 and below and the consistently low oral acute toxicity for the category as a whole it is expected that aliphatic alcohols in the range C18 – C22 are of a low order of acute dermal toxicity.

Clinical signs.Occluded exposure for 24 hours generally caused local dermal irritation. There was a clear (inverse) relationship between the chain length and the severity of the dermal effects. The severity of the irritation was graded as moderate – severe for the lower members of this category; typical observations included erythema, oedema, wrinkling, desquamation and cracking. The grading of the local effects for the aliphatic alcohols with a longer carbon chain was reported as slight-moderate. Animals showing signs of significant local irritation displayed signs of toxicity such as general weakness, anorexia, lethargy; it is not possible to ascertain if these findings were secondary to the irritation or evidence of direct systemic toxicity. 

Conclusion:The category of the long chained aliphatic alcohols is of a low order of acute toxicity upon dermal administration. Alcohols, C16-18 was not classified according to EU or GHS criteria.

 

 

 

Justification for classification or non-classification

Based on the hazard assessment of Alcohols, C16-18 in section 2.1 and 2.2. in IUCLID 5.4., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health”, according to the EU’s list of dangerous substances (OJEC No L200/130.7.99)and according to the criteria described in Directive 67/548 and in the CLP Regulation:

Directive 67/548

Very Toxic (T+) R28: Very toxic if swallowed R27: Very toxic in contact with skin R26: Very toxic by inhalation R39/26 R39/27 R39/28: Dangerous of very serious irreversible effects Toxic (T):  R25: Toxic if swallowed R24: Toxic in contact with skin R23: Toxic by inhalation R39/23 R39/24 R39/25: Danger of very serious irreversible effects Harmful (Xn): R22: Harmful if swallowed R21: Harmful in contact with skin R20: Harmful by inhalation R65: Harmful may cause lung damage if swallowed R21/22 Harmful; Harmful in contact with skin and if swallowed. R68/20 R68/21 R68/22: Possible risk of irreversible effects Other toxicological properties R67: Vapours may cause drowsiness and dizziness

CLP

H300 Acute Tox. 2 Fatal if swallowed H310 Acute Tox. 1 Fatal in contact with skin H330 Acute Tox. 2 Fatal if inhaled H370 STOT SE 1 H301 Acute Tox. 3 Toxic if swallowed H311 Acute Tox. 3 Toxic in contact with skin H331 Acute Tox. 3 Toxic if inhaled H370 STOT SE 1 H302 Acute Tox. 4 Harmful if swallowed H312 Acute Tox. 4 Harmful in contact with skin H332 Acute Tox. 4 Harmful if inhaled H304 Asp. Tox. 1 H371 STOT SE 2 (May cause damage to organs (or state all organsaffected if known) (state route of exposure if it is conclusively proventhat no other routes of exposure cause the hazard) Other toxicological properties H336 STOT SE 3 May cause drowsiness or dizziness

It is concluded that the substance Alcohols, C16-18 does not meet the criteria to be classified for human health hazards for acute oral effects