Decan-1-ol

Endpoint summary

Description of key information

The key acute oral toxicity study with decan-1-ol in rat, conducted according to a protocol similar to OECD Test Guideline 423 and in compliance with GLP, reports an LD50 value of >5000 mg/kg bw (Eurofins 2009; rel 1).

The key acute inhalation toxicity study with decan-1-ol, conducted prior to OECD Test Guideline and GLP, reported an LC50 of >71mg/L in rats, following 1-hour whole body inhalation exposure to the atmosphere generated as a mist (Scientific Associates 1977; rel 2).

The key acute dermal toxicity study with decan-1-ol, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of >5000 mg/kg bw in rat (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)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

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 acute oral toxicity study with decan-1-ol in rat, conducted according to a protocol similar to OECD Test Guideline 423 and in compliance with GLP, reports an LD50 value of >5000 mg/kg bw.

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 acute inhalation toxicity study with decan-1-ol, conducted prior to OECD Test Guideline and GLP, reported an LC50 of >71mg/L in rats, following 1-hour whole body inhalation exposure to the atmosphere generated as a mist.

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)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (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 acute dermal toxicity study with decan-1-ol, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of >5000 mg/kg bw in rat.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

The key acute oral toxicity study with decan-1-ol in rat, conducted according to a protocol similar to OECD Test Guideline 423 and in compliance with GLP, reports an LD50 value of >5000 mg/kg bw (Eurofins 2009; rel 1). In the study, undiluted decan-1-ol was administered orally by gavage to female rats at doses of 175 mg/kg bw, 550 mg/kg bw, 1750 mg/kg bw or 5000 mg/kg bw. 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. At the end of the 14-day observation period, all the animals were subject to necropsy. No mortality occurred during the 14-day observation period. 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 5000 mg/kg bw following administration all females exhibited ano-genital staining and one female also exhibited soft faeces. All animals recovered by day 2 and appeared active and healthy for the remainder of the study. All animals gained body weight during the study. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

The oral LD50 values of the supporting studies are in accordance with that of the key study, all residing at or above 5000 mg/kg and ranging up to >26410 mg/kg. The key study for oral toxicity reports no treatment related clinical signs with no remarkable findings at necropsy. Most of the supporting studies are in accordance with these findings, however Scientific Associates Inc. (1977, rel 2) report the following effects in animals which succumbed: congestion of the kidneys, adrenals, liver, lungs, stomach and gastrointestinal tract, and erosion of the mucosal tissue of the stomach and depletion of visceral fat, identifying the stomach and mucosal lining as potential target organs.

The key acute inhalation toxicity study with decan-1-ol, conducted prior to OECD Test Guideline and GLP, reported an LC50 of >71mg/L in rats, following 1-hour whole body inhalation exposure to the atmosphere generated as a mist (Scientific Associates 1977; rel 2). In the study, 5 rats were exposed to decan-1-ol atmosphere generated as a mist at a concentration of 71 mg/L by whole body inhalation exposure for 1 hour. The animals were observed for gross effects at regular intervals on the day of exposure and daily thereafter for 14 days. All animals were weighed at the beginning and end of the test period. At the end of the 14-day observation period, all the animals were subject to necropsy. All rats survived the 1-hour exposure and subsequent 14-day observation period. 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 showed reddened encrustation about the eyes, nose and roughened coat. Final bodyweight records of the animals at termination (14 days) showed gains within expected limits, in all animals. Gross necropsy of the animals at 14 days showed slight to moderate pulmonary (all animals) and adrenal (two animals) congestion. All other findings were unremarkable.

In another acute inhalation toxicity study with decan-1-ol, conducted according to a protocol similar to OECD Test Guideline 403 and in compliance with GLP, an LC50 value of > 2.05 mg/L air following 4-hour nose only inhalation exposure to the decan-1-ol vapour was reported (Eurofins, 2008). In the study, 5 male and 5 female rats were exposed to decan-1-ol vapours at a concentration of 2.05 mg/L (gravimetric) by nose only inhalation for 4 hours. All animals were observed for mortality during the exposure period. The animals were examined for signs of gross toxicity and behavioural changes upon removal from the exposure tube and at least once daily thereafter for 14 days. At the end of the 14-day observation period, all the animals were subject to necropsy. No mortality occurred during the 14-day observation period. Following exposure all animals were hypoactive and exhibited abnormal respiration, hunched posture and/or nasal discharge. However, all  animals recovered by day 7 and appeared active and healthy for the remainder of the 14-day observation period. All animals gained bodyweight over the 14-day observation period. No gross abnormalities were noted in for the animals when necropsied at the conclusion of the 14-day observation period.

The key inhalation study (Scientific Associates Inc. 1977, rel 2) necropsy findings reveal slight to moderate pulmonary and adrenal congestion, with affected lungs but otherwise unremarkable overall necropsy findings. The supporting studies are sparse in detail and one study (Potokar, 1979) was disregarded due to deficiencies in study design and reporting.The key study for acute inhalation (Scientific Associates, 1977) was selected over the more recent one (Eurofins, 2008; rel 1) study as the LC50 of >2.05 mg/l result reported is insufficient for classification purposes as a result of too low an exposure level.

The key acute dermal toxicity study with decan-1-ol, conducted according to a protocol similar to OECD Test Guideline 402 and in compliance with GLP, reports an LD50 value of >5000 mg/kg bw in rat (Eurofins 2009; rel 1). In the study, 5000 mg/kg bw of undiluted decan-1-ol was applied onto the skin of 5 male and 5 female rats for 24 hours. 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. At the end of the 14-day observation period, all the animals were subject to necropsy. No mortality occurred during the 14-day observation period. 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. All animals gained body weight during the study period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

For acute dermal toxicity, one of the supporting studies (Scientific Associates 1976, rel 2) reports the gastric mucosa as a potential target organ with signs of topical irritation. The LD50 value of a reliability 2 dermal supporting study (Potokar 1979, rel 2) is >1000 mg/kg (the highest dose tested), with no necropsy findings reported.

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. 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 and considerations of RAAF Assessment Entities can be found in the Human Health Alcohols C6-24 Category report (PFA, 2016).

Justification for classification or non-classification

Based on reliable oral, dermal and inhalation data, decan-1 -ol is not classified for acute toxicity in accordance with EC Regulation 1272/2008.