Alcohols, C9-11-branched and linear

Endpoint summary

Description of key information

There are acute oral and dermal toxicity studies for Alcohols, C9-11 branched and linear. There is no acute inhalation toxicity study for Alcohols, C9-11 branched and linear, therefore the key acute inhalation toxicity study is read-across from Alcohols, C9-11.

The key acute oral toxicity study for Alcohols, C9-11 branched and linear, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an LD50 value of >4000 mg/kg bw (Albert, 1981a; rel 1).

The key acute dermal toxicity study for Alcohols, C9-11 branched and linear, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of >1660 mg/kg (Albert 1981b; rel 1).

The key acute inhalation toxicity study for the analogue Alcohols, C9-11, conducted according to a protocol similar to OECD Test Guideline 403, but without information on GLP compliance, reports an LC50 value of >0.237  mg/l following 4-hour inhalation exposure to the vapour of Alcohols, C9-11 (Blair 1981; 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:

03.11.1980-

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Method: other: regulatory procedure

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Portage, Michigan, US
- Age at study initiation: Not reported.
- Weight at study initiation: males 213.9 + or - 8.1g; females 170 + or -  10.4 g (fasted weights for treated animals)
- Fasting period before study: overnight
- Housing: individual polycarbonate/wire mesh cages
- Diet: ad libitum, except during exposure
- Water: yes, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average 23.3
- Humidity (%): average 54.9
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5ml/kg

Doses:

5 ml/kg

No. of animals per sex per dose:

5M, 5F

Control animals:

yes

Remarks:

5M+5F receiving 5 ml/kg distilled water.

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed:  All rats were necropsied at the end of the  observation period.
- Other examinations performed: Clinical signs were recorded hourly for 6 hours after  dosing then at 24 hours and twice daily throughout the 14-day observation  period.  Body weights were recorded the day before dosing and at 7 and 14 days. A fasted body weight was taken prior to dosing and used for  calculation of the dosage.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 4000 mg/kg bw based on the lower value of density range, 0.8 g/cm3)

Mortality:

There were no mortalities in either test or control animals.

Clinical signs:

other: All treated animals had diarrhoea at 0.5 -1.5 hours after  dosing, while 4/5 males and all females had polyuria by 24 hours after  dosing. Among control animals one female had polyuria. All animals  appeared normal by 54 hours post-dosing. The only other 

Gross pathology:

There was no observable pathology in either test or  control animals.

Other findings:

POTENTIAL TARGET ORGANS: No conclusions.
SEX-SPECIFIC DIFFERENCES: None

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity study for Alcohols, C9-11 branched and linear, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an LD50 value of >4000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29.09.1977-20.01.1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Method: other: in house protocol

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: hell Toxicology Laboratory (Tunstall) Breeding Unit,  Sittingbourne, Kent, UK
- Age at study initiation:  11 weeks approx
- Weight at study initiation: males 327-391g; females 190-240
- Housing: initially the animals were segregated into equal weight distribution groups, but after exposure the animals were individually housed in hanging polypropylene cages with stainless steel wire mesh floor and top.
- Diet: ad libitum
- Water: tap water, ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 20
- Humidity (%): ca. 55
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: vapours

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: tubular glass chambers
- Exposure chamber volume: 5 litres
- Method of holding animals in test chamber: stainless steel mesh carriers, accommodating 5 animals each
- Source and rate of air: 10 litres/minute
- System of generating particulates/aerosols: the test atmosphere was generated by means of a wick-type saturator maintained at 42C in a thermostat water bath and were supplied to two identical glass inhalation chambers each of volume 5 litres.


TEST ATMOSPHERE
- Brief description of analytical method used: The atmospheric concentration of the test material was measured continuously throughout the exposure by means of a total hydrocarbon analyser fitted with a flame ionisation detector.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

Two separate exposures were made as follows firstly to  an atmosphere containing 0.212 mg/l of the more volatile components of  Dobanol 91 and secondly to an atmosphere containing 0.237 mg/l of the  less volatile components (atmospheres were analysed continuously  throughout exposure using a total carbon analyser and flame ionisation  detector). In both cases the test atmospheres were near saturated.

No. of animals per sex per dose:

5M+5F/group  

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs were continuously observed for the first 30  minutes of exposure then at 15-minute intervals throughout exposure and  twice daily thereafter throughout the 14-day observation period. Initial  and terminal bodyweights were recorded. Gross post mortem examination was carried out on all animals.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.237 mg/L air

Exp. duration:

4 h

Mortality:

All animals survived the 4 hour exposure period and subsequent  14 day observation period.

Clinical signs:

other: No signs of toxicity. All animals gained weight normally  over the observation period.

Body weight:

The body weight gains were within normal limits.

Gross pathology:

None reported.

Other findings:

POTENTIAL TARGET ORGANS: None identified.
SEX-SPECIFIC DIFFERENCES: None observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation toxicity study for the analogue Alcohols, C9-11, conducted according to a protocol similar to OECD Test Guideline 403, but without information on GLP compliance, reports an LC50 value of >0.237 mg/l following 4-hour inhalation exposure to the vapour of Alcohols, C9-11.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE CATEGORY APPROACH
The hypothesis is that the category members have similar structures and properties (absence of acute inhalation toxicity effects), which are consistent across the category (Scenario 6 in the RAAF). The consistency of this property across the category is discussed in the endpoint summary.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to the test material identity information within each endpoint study record.

The long chain linear aliphatic alcohol Category has at its centre a homologous series of increasing carbon chain length alcohols. The category members are structurally very similar. They are all primary aliphatic alcohols with no other functional groups. The category members are linear or contain a single short-chain side-branch at the 2-position in the alkyl chain, which does not significantly affect the properties (‘essentially linear’). The category members have saturated alkyl chains or contain a small proportion of naturally-occurring unsaturation(s) which does not significantly affect the properties. The branched and unsaturated structures are considered to have such similar properties that their inclusion in the category is well justified.
Impurities: Linear and/or ‘essentially linear’ long chain aliphatic alcohols of other chain lengths may be present. These are not expected to contribute significantly to the properties in respect of this endpoint due to consistent properties (see point 3).
There are no impurities present at or above 1% which are not category members or which would affect the properties of the substance.

3. CATEGORY JUSTIFICATION
The category members are structurally very similar (see point 2) and are biochemically very similar. The metabolic synthesis and degradation pathways are well established. This Category is associated with a consistency and predictability in the physicochemical, environmental, and toxicological property data across its members.

The consistency of observations in this property across the range of chain lengths covered by this Category is described in the Endpoint Summary and in the Category Report attached in Section 13.

In this registration, the information requirement is based on read-across from members of the category with similar chain length. Data from substances across the category provides evidence of consistency in effects irrespective of variation in physico-chemical properties of specific category member substances.

4. DATA MATRIX
A data matrix for the C6-24 alcohols Category is attached in Section 13.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.237 mg/L air

Exp. duration:

4 h

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 370 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

Study period:

1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Method: other: in house protocol

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Camm Research Institute, Wayne, New Jersy, USA
- Age at study initiation: Not reported
- Weight at study initiation: average weight 3.10 kg
- Fasting period before study:
- Housing: individual cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4 weeks



ENVIRONMENTAL CONDITIONS
- Temperature (°C): average 20.2
- Humidity (%): average 46.3
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back/trunk
- % coverage: 4X4 inches
- Type of wrap if used: Gauze plus impervious wrap (Saran) and elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Remaining material removed using a moist  towel.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2ml/kg

Duration of exposure:

24 hours on intact and abraded skin

Doses:

2 ml/kg

No. of animals per sex per dose:

- Group size: 4M+4F
- Controls: 4M+4F

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality and clinical signs were made at  1,2,4,6 and 24 hours after application and then twice daily through out  the 14 day observation period. Body weights were measured on days -1, 0,  7 and 14. 
- Necropsy of survivors performed: yes
- Other examinations performed:  Each exposure site was scored (Draize)  for degree of irritation immediately on removal of the dressings and  prior to termination on day 14. 

Statistics:

calculation of mean and standard  deviation. Determination of the significance of bodyweight changes  compared to controls was made using an independent T-test.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 660 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the exposure and 14 day observation  period. The dermal LD50 is therefore >2 ml/kg, this is equivalent to 1660  mg/kg using a density of 0.83 for conversion.

Clinical signs:

other: There were no treament related signs of toxicity.  There was minimal skin irritation at the 24 hour period  for both intact and abraded skin. Mean erythema and oedema scores for  intact skin were 1.9 and 1.1 respectivley compared to 0.2 and 0.1 in the  co

Gross pathology:

The presence of white flaky material at the  application site was the only remarkable finding.

Other findings:

POTENTIAL TARGET ORGANS: None identified.
SEX-SPECIFIC DIFFERENCES: None observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal toxicity study for for Alcohols, C9-11 branched and linear, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of >1660 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

1 660 mg/kg bw

Additional information

There are acute oral and dermal toxicity studies for Alcohols, C9-11 branched and linear. There is no acute inhalation toxicity study for Alcohols, C9-11 branched and linear, therefore the key acute inhalation toxicity study is read-across from Alcohols, C9-11.

The key acute oral toxicity study for Alcohols, C9-11 branched and linear, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401 and in compliance with GLP, reports an LD50 value of >4000 mg/kg bw (Albert, 1981a; rel 1). In the study, male and female rats were given single oral administration by gavage 5 ml/kg bw (equivalent to 4000 mg/kg bw based on density of 0.8 g/cm3) undiluted Alcohols, C9-11 branched and linear. The animals were observed for 14 days. All rats were necropsied at the end of the  observation period. Body weight and clinical signs were monitored during the study duration. No mortality occurred during the 14-day observation period. All treated animals had diarrhoea at 0.5 - 1.5 hours after  dosing, while 4/5 males and all females had polyuria by 24 hours after  dosing. Among control animals one female had polyuria. All animals  appeared normal by 54 hours post-dosing. The only other observation considered treatment related was hypoactivity in 2 rats during the first 3 hours after dosing.  The rats of both treated and control groups gained  in body weight over the 14-day observation period and there were no  treatment related differences in body weight gain. The were no test substance-related findings at necropsy.

The findings of the key study are supported by data for the analogue Alcohols, C9-11. In the acute oral toxicity study for Alcohols, C9-11, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401, but prior to GLP, an LD50 value of >8300 mg/kg bw was concluded following single oral gavage administration of 10 ml/kg bw of undiluted test material. No mortality occurred during the study period. Diarrhoea was the only clinical sign observed. (Shell, 1978).

The key acute dermal toxicity study for Alcohols, C9-11 branched and linear, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of >1660 mg/kg bw (Albert 1981b; rel 1). In the study, 2 ml/kg bw (equivalent to 1660 mg/kg bw based on density of 0.8 g/cm3) of undiluted Alcohols, C9-11 branched and linear were applied onto the intact or abraded skin of male and female rats under occlusive dressing for 24 hours. Following the 24-hour exposure period, the remaining test material was removed by using a moist towel. The animals were observed for 14 days. All rats were necropsied at the end of the  observation period. Body weight and clinical signs were monitored during the study duration. No mortality occurred during the 14-day observation period. There were no treatment related signs of toxicity.  There was minimal skin irritation at the 24-hour period  for both intact and abraded skin. Mean erythema and oedema scores for  intact skin were 1.9 and 1.1 respectively compared to 0.2 and 0.1 in the  controls. For abraded skin erythema and oedema scores were 2 and 1  respectively with control values of 0.6 and 0.1. The presence of white flaky material at the  application site was the only remarkable finding. No irritation was  evident at study day 14.  Bodyweights in treated animals were comparable to those of controls. Based on the study findings and data on acute dermal toxicity across category on alcohols of this chain length, it is concluded that no mortalities would have occurred at the application of 2000 mg/kg bw of the test substance.

The findings of the key study are supported by data for the analogue Alcohols, C9-11. In the acute dermal toxicity study for Alcohols, C9-11, conducted according to a protocol similar to OECD Test Guideline 402, but prior to GLP, an LD50 value of >1660 mg/kg bw was concluded following 24-hour occluded dermal application of 2 ml/kg bw undiluted test material. No mortality, dermal irritation, clinical effects, or organs changes occurred for any of the test animals (Shell, 1978).

The key acute inhalation toxicity study for the analogue Alcohols, C9-11, conducted according to a protocol similar to OECD Test Guideline 403, but without information on GLP compliance, reports an LC50 value of >0.237  mg/l following 4-hour inhalation exposure to the vapour of Alcohols, C9-11 (Blair 1981; rel 2). The LC50 value for acute inhalation represents a near saturated vapour concentration and is therefore deemed suitable for determining classification and labelling outcome. All animals survived the 4-hour exposure period and subsequent 14-day observation period. No signs of toxicity were noted. All animals gained weight normally over the observation period. The body weight gains were within normal limits. No changed during necropsy were reported.

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. The available data for the Category have been reviewed with the conclusion that the long chain alcohols are of a low order of acute oral and dermal toxicity, and the inhalation LC50 is expected to be greater than the substantially saturated vapour concentration (Veenstra G, Webb C et al., 2009). 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. A full discussion of the Category can be found in the Human Health Alcohols C6-24 Category report (PFA, 2016).

Justification for classification or non-classification

The available acute toxicity data for Alcohols, C9-11 branched and linear do not indicate any potential hazard for acute, dermal or inhalation toxicity. Tests on similar substances included in this category are also supportive of these results which do not warrant classification for any acute toxicity endpoint under CLP or GHS criteria. The substance is therefore not classified for acute toxicity according to Regulation (EC) No 1272/2008.