Nonan-1-ol

Endpoint summary

Description of key information

All the acute toxicity key studies are read across from decanol (112-30-1). The acute oral key study in rat reports an LD50 value of >5000 mg/kg (Eurofins 2009; rel 1). The acute inhalation key study in rat exposed the animals to atmosphere generated as mist for 1 hour, with a result of LC50 >71mg/L (Scientific Associates 1977; rel 2). The acute dermal key study in rat reports an LD50 value of >5000 mg/kg (Eurofins 2009; rel 1).

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:

2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals Inc., Boyertown, PA
- Age at study initiation: Young adult (10-12 weeks)
- Weight at study initiation: 183-210 g


ENVIRONMENTAL CONDITIONS
- Temperature (°C):19-21C
- Humidity (%): 63-87

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

175mg/kg, 550 mg/kg, 1750mg/kg, 5000mg/kg

No. of animals per sex per dose:

175mg/kg (1 animal), 550 mg/kg (1 animal), 1750mg/kg (1 animal), 5000mg/kg (3 animals)

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 mortality, signs of gross toxicity and behavioural changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing. OBservations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Tissues and organs of the thoracic and abdominal cavities were examined.

Statistics:

The acute oral toxicity (Guideline 425) Statistical Program (Westat, version 1.0 May 2001) was used for all data analyses including dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities.

Clinical signs:

other: All animals appeared active and healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour at the lower doses, however at the 5000mg/kg following administration all females exhibited ano-genital st

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14 day observation period.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value of >5000mg/kg is reported in a reliable study conducted according to an appropriate guideline. The study was also compliant with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 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

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: other: contract laboratory protocol

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: COX-CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 216 to 253 grams

- Housing: Glass chamber for the duration of exposure to the test substance which after the animals were placed in individual wire-bottomed cages elevated above droppings.

- Diet: Purina laboratory Chow, pelletized (ad libitum)

- Water: ad libitum



IN-LIFE DATES: Not stated.

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: shared glass chamber

- Source and rate of air: six litres per minute


TEST ATMOSPHERE

- Brief description of analytical method used: non specified

- Samples taken from breathing zone: not specified



CLASS METHOD (if applicable)

- Rationale for the selection of the starting concentration:

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

1 h

Concentrations:

71 mg/l

No. of animals per sex per dose:

5

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, body weight,organ weights, histopathology, other: The animals were observed for gross effects at regular intervals on the day of exposure and daily thereafter for fourteen days. All animals were weighed at the beginning and end of the test period.

Statistics:

No statistical analysis performed.

Preliminary study:

No preliminary study.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 71 mg/L air

Exp. duration:

1 h

Mortality:

All rats survived the 1 hour exposure and subsequent 14 day  observation period.

Clinical signs:

other: During exposure, all animals displayed hypoactivity and/or ataxia, salivation and gasping. Generalised weakness was also evident when the animals were removed from the chamber at the end of the exposure. At the 24 hour observation period, all animals show

Body weight:

Final bodyweight records of the animals at termination (14 days) showed gains within expected limits, in all animals.

Gross pathology:

Gross necropsy of the animals at fourteen days showed slight to moderate pulmonary (all animals) and adrenal (two animals) congestion; otherwise findings were unremarkable.

Other findings:

The lungs were affected in all rats.

Table 1: Concentrations, exposure conditions and number of evident toxicity per animals treated.

Nominal Conc. (mg/L)	Number with evident toxicity (#/total)
	Males	Females	Combined
71	0/5	0/5	0/10

 

Interpretation of results:

GHS criteria not met

Conclusions:

The result was read across from 1-decanol. The rat 1 hour LC50 for Alfol 10 (mist) was >71 mg/l. Signs of intoxication during exposure included lethargy,and/or ataxia, salivation and gasping. Gross necropsy revealed congestion of the lungs in all animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

71 000 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

Study period:

2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Principles of method if other than guideline:

The humidity was below the targeted lower limit of 30% during the study. A portable humidifier was used to increase the humidity levels during this time.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace animals Inc., Boyertown, PA
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 221-236g males, 182-200g females
- Housing: singly housed in suspended stainless steel caging with mesh floors
- Diet: Purina rodent chow, ad libitum
- Water: filtered tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 19-52
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk
- % coverage: 10
- Type of wrap if used: the gauze pad under which the test material resided was wrapped with tape to avoid dislocation of the pad and to minimize loss of the test substance.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test sites were gently cleansed with a 3% soap solution followed by ethanol then tap water using a clean paper towel to remove any residual test substance
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): individual doses were calculated based on the initial body weights, taking into account the specific gravity of the test substance.

Duration of exposure:

24 hours

Doses:

5000mg/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: Individual body weights were recorded prior to test substance application (initial) and again on days 7 and 14. The animals were observed for mortality, signs of gross toxicity, and behavioural changes during the first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Tissues and organs of the thoracic and abdominal cavities were examined.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities.

Clinical signs:

other: Other than the dermal irritation noted at all dose sites between days 1 and 12, there were no other clinical findings recorded for any animal over the course of the study.

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14 day observation period.

Erythema, desquamation and hyperkeratosis were present at the dose site.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 value of >5000 mg/kg is reported in a reliable study conducted according to an appropriate guideline. The study was compliant with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

The acute toxicity key results are read across from decanol (CAS 112 -30 -1) based on the notion that the available acute toxicity across category is found to be low. The available reliability 4 supporting studies for nonan-1-ol for each of these endpoints further support the read across results.

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

Based on the available information it is proposed that nonan-1-ol will not be classified for acute oral, inhalation or dermal toxicity in accordance with CLP (EC regulation 1272/2008).