Registration Dossier

Administrative data

Description of key information

oral:
All the LD50 values of the test substance and category members were found to be greater than 2000 mg/kg bw.
inhalation:
No mortalities occured when the substances were applied as vapour. In a study conducted on pentanol, branched and linear, which was applied as an aerosol, the LC50 in mice was found to be > 14 mg/L.
dermal:
All the dermal LD50 value were found to be greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 690 mg/kg bw
Quality of whole database:
reliable studies conducted similar to OECD Guideline, sufficient for assessment

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
14 000 mg/m³
Quality of whole database:
well documented study reports and publications, sufficient for assessment

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 160 mg/kg bw
Quality of whole database:
reliable studies conducted similar to OECD Guideline, sufficient for assessment

Additional information

Acute toxicity

 

Oral route

Acute oral toxicity of pentanol, branched and linear was evaluated. Each 5 male Carworth-Wistar rats were administered with 2520, 3160, 3980 and 5000 mg/kg bw pentanol, branched and linear in corn oil by gavage. The rats were prostrated at 5000 mg/kg bw and had tremors at 2500 mg/kg bw. Autopsies revealed congested or hemorrhaged lungs, mottled livers, gastrointestinal tract irritation, and surface burning of the kidney and adrenal where they contacted the gastrointestinal tract. A LD50 of 3900 mg/kg bw was estimated (95 % CL: 3300-4500) (UCC 1955).

Another study with branched and linear pentanols was performed. In this study five male Sprague-Dawley rats per dose received a mixture of 75 % wt 1-Pentanol, 25 % wt 2-methyl-1-butanol, 1 % wt 3-methyl-1-butanol at doses of approx. 26.1 - 8155 mg/kg bw by gavage. After dosing, central nervous system depression and laboured respiration were noted and the recovery was completed by the second or third day. Due to observed mortality occurring within 24 hours, a LD50 of 2690 mg/kg bw was calculated (Scala & Burtis 1973).

Acute oral toxicity of the read -across substance 2-methyl-1-butanol was evaluated similar to OECD guideline 401. Groups of 5 male and 5 female Sprague-Dawley rats received doses of 1470, 2150, 3160 and 5000 mg/kg bw 2-methyl-1-butanol as 14.7, 21.5, 31.6 and 50 % solution in carboxymethyl cellulose by gavage treatment. At 5000 and 3160 mg/kg bw 8/10 and 1/10 animals died within one day after administration, respectively. Clinical signs included dyspnoea, apathy, abnormal/lateral position, staggering, paresis/atonia, pain and absent corneal reflex, piloerection and poor general state. At necropsy, acute congestive hyperemia in the heart and cardiodilatation were detected in the deceased animals. Due to the observed mortality in the higher dose groups, the LD50 value of approx. 4172 mg/kg bw was estimated (BASF AG 1979).

Acute oral toxicity of the read-across substance 3-methylbutan-1-ol was evaluated in a study which was performed similar to the methods described in OECD guideline 401. Groups of 5 male and 5 female Sprague-Dawley rats received doses of 2150 and 5000 mg/kg bw 3-methylbutan-1-ol in carboxymethyl cellulose by gavage treatment. Up to 5 hours after treatment clinical symptoms including dyspnoea, apathy, abnormal position, staggering, erythrodermia and poor general state were observed in both dose groups. In both dose groups 1/5 females died, whereas all males survived until study termination. At necropsy, acute congestive hyperemia in the heart and cardiodilatation were observed in the deceased animals. The LD50 was estimated to be > 5000 mg/kg bw (BASF AG 1979).

Acute oral toxicity of the read-across substance pentan-1-ol was evaluated in a study similar to OECD guideline 401. Groups of 5 male and 5 female Sprague-Dawley rats were dosed with approx. 162, 1296, 2592, 3240, 4050, 5184, 6480 and 8100 mg/kg bw pentan-1-ol in carboxymethyl cellulose by gavage. In the 2592 mg/kg bw and higher dose groups clinical signs including staggering, atonia, apathy, narcosis and tachypnea were noted. At the two low dose levels no mortalities occurred. In the higher dose groups at 2592, 3240, 4050 and 5184 mg/kg bw 3/10, 2/10, 8/10 and 9/10 animals were found dead within 24 hrs. In the two highest dose groups all animals died within one hour after administration. At necropsy, venous congestive hyperemia and acute cardiodilatation were observed in the deceased animals. The LD50 was estimated to be approx. 3645 mg/kg bw (BASF AG 1973)

A further study is available which was conducted with the read-across substance pentan-1-ol. Male Wistar rats were administered with approx. 3258, 6515 and 13030 mg/kg bw pentan-1-ol by gavage. Clinical signs of intoxication included unsteady gait, prostration, and heavy breathing. Gross pathology in animals that died included stomachs transparent, distended, injected, gas or fluid-filled; medullae of kidneys pink; intestines transparent or pink, injected, fluid-filled. Due to the observed mortality a LD50 of 4610 mg/kg bw was estimated (UCC 1978).

A study is available which was conducted with 2-methyl-1-butanol. 5 male albino rats were administered with approx. 1632, 3264 and 6528 mg/kg bw 2-methyl-1-butanol by gavage. Mortality was observed in all rats dosed with 6528 mg/kg bw within a day of dosing. One of 5 rats dosed with 3264 mg/kg bw died on the day of dosing. All other rats dosed with 3264 mg/kg bw as well as rats dosed with 1632 mg/kg bw survived the 14 day observation period. Surviving rats gained 36-60 g bw during the 14 day observation period. Gross pathology on the rats dosed with 6528 mg/kg bw revealed congested or hemorrhaged lungs, mottled or chemically burned livers, spleens and stomachs, mottled or pale kidneys, congested adrenals and gastrointestinal tract irritation or hemorrhage. Due to the observed mortality a LD50 of 4015 mg/kg bw was estimated (95 % CL: 3044-5271; calculated based on rel. density = 0.816) (UCC 1959).

Another oral toxicity study of the read-across substance 3-methylbutan-1-ol was conducted according to methods described by Smyth HF et al. (Am. Ind. Hyg. Assoc. J. 23, 95, 1962). Groups of 5 male and 5 female Carworth-Wistar rats received a logarithmic series of doses differing by a factor of two of 3-methylbutan-1-ol by gavage treatment. The animals were observed for 14 days. The LD50 value and its fiducial range were estimated by the method of Thompson (1947) using the tables of Weil (1952). The LD50 was estimated to be ca. 5726 mg/kg bw (95 % CL: 3856-8424; calculated based on density = 0.81 g/cm3) (Smyth 1969).

 

In several further abstracts LD50 values in rats of greater 2000 mg/kg bw in rats were confirmed. The LD50 in mice was reported as 3000 mg/kg bw, while no guinea pig died up to approx. 650 mg/kg bw. No further details are available.

As a conclusion, the acute oral toxicity of Pentanol is low.

 

Inhalation route

An inhalation hazard test is available for branched and linear pentanols (UCC 1955). When groups of 6 male rats were exposed to an atmosphere saturated with vapours of a mixture of pentan-1-ol and 2-methylbutan-1-ol for 8 hours, no mortality was observed. The only notable response was light anesthesia after 1.5 hours of exposure. All rats were active a few seconds after cessation of the exposure.

Valid aerosol studies in rats, mice and guinea pigs were conducted with an isomer mixture equivalent to pentanol, branched and linear and are taken into consideration. Groups of 10 Wistar rats, 10 Swiss mice and 10 English Short Hair guinea pigs were exposed to an aerosol of 14 mg/L amyl alcohol consisting of 75 % wt pentanol-1-ol, 25 % wt 2-methyl-1-butanol and 1 % wt 3-methyl-1-butanol (Scala & Burtis 1973). As a consequence of mortality (2/10), the LC50 of > 14 mg/L air was determined in rats, whereas in mice the LC50 was < 14 mg/L air (7/10). Since in the study with guinea pigs no mortality occurred (0/10), the effect level for this species was LC0 = 14 mg/L air. Clinical signs included prostration and irritation of mucous membranes of the eyes, nose, throat and respiratory passage. Histological examination of trachea, lung, liver, and kidney from the exposed animals revealed an increase in the size of the deep proximal convoluted tubules associated with an increased size of the epithelial cells lining the tubules. Pulmonary oedema was noted in the mice.

An inhalation hazard test (IHT) according to the method described in the Annex of OECD TG 403 (1981) was conducted to assess the acute inhalative toxicity of the read-across substance 2-methylbutan-1-ol. Three male and three female Sprague-Dawley rats were exposed (whole body) to a saturated vapour atmosphere of 2-methyl-1-butanol for 7 hours. Since no mortality and no remarkable adverse effects were observed, the experiment was repeated once. A nominal LC0 of 12.28–16.61 mg/L air could be calculated using the weight loss of the substance during the exposure period (BASF AG 1979).

Acute inhalative toxicity of the read-across substance 3-methylbutan-1-ol was investigated in an inhalation hazard test (IHT) according in principle to the method described in the Annex of OECD TG 403 (1981), where three male and three female Sprague-Dawley rats were exposed to a saturated vapour atmosphere of 3-methylbutan-1-ol (whole body) for 7 hours (BASF AG 1979). The only clinical signs observed were intermittent respiration during the first few minutes of exposure and a loss of pain reflex up to 4 hours after start of the exposure. Otherwise, no mortality and no remarkable adverse effects were observed. Thus, the LC0 was 11.05 mg/L air based on the weight loss of the substance during the exposure period.

Acute inhalative toxicity to the read-across substance pentan-1-ol was also examined in an inhalation hazard test (IHT) equivalent to the method described in the Annex of OECD TG 403 (1981), where three male and three female Sprague-Dawley rats were exposed (whole body) to a saturated atmosphere of pentan-1-ol vapours for 8 hours (BASF AG 1973). Since no mortality and no remarkable adverse effects were observed, the LC0 of 8.29 mg/L air could be calculated using the weight loss of the substance during the exposure period.

Another test using 2-methylbutan-1-ol was conducted (UCC 1959). A group of 6 CFN female rats were exposed with the whole body to a concentration of 3427 ppm (= 12.53 mg/L) of the vapour in air for 8 hours. During the 14 days observation period no mortality was detected. Two rats were prostrate after 6 hours and 3 were anesthetized after 8 hours. The others had poor coordination of body movements. All survived and gained weight during the observation period. Therefore a LC0 was established at 12.53 mg/L air (nominal) and 3427 ppm.

This is supported by another inhalation hazard test where no mortality was observed either, when six male Wistar rats were exposed for 8 hours to an atmosphere that was essentially saturated with test substance vapours (UCC 1978).

Another inhalative toxicity study (IHT) of 3-methylbutan-1-ol was conducted according to methods described by Smyth HF et al. (Am. Ind. Hyg. Assoc. J. 23, 95, 1962). 6 male and 6 female albino rats were exposed with the whole body to a concentrated vapour in air for 8 h. Afterwards animals were observed for 14 days. No mortality was detected. The LC0 was estimated at 10 mg/L air (calculated acc. to formula: vapour saturation (mg/L) = 0.0412 * vapour pressure (hPa) * molecular weight (g/mol)) (Smyth 1969).  

An additional acute inhalative toxicity study (Alarie assay) with pentan-1-ol was conducted using 4 male Swiss Webster mice. The vapour-aerosol mixture was proposed with a concentration of 14.8 mg/L. Animals were exposed head only for 10 min. The RD 50 was estimated at 14.8 mg/L air (nominal) and at 4039 ppm (95 % CL: 3113-6033) (Kane 1980).

An additional acute inhalative toxicity study (Alarie assay) with 3-methylbutan-1-ol was conducted using 4 male Swiss Webster mice. The vapour-aerosol mixture was proposed with a concentration of 16.28 mg/L. Animals were exposed head only for 10 min. The RD 50 was estimated at 16.28 mg/L air (nominal) and at 4452 ppm (95 % CL: 2885-12459) (Kane 1980).  

Another study of 3-methylbutan-1-ol investigated the acute toxicity using an inhalation hazard test (Alarie assay). Mice were exposed via vapour in air. The RD 50 (50% decrease in respiratory rate) was estimated at 2.63 mg/L air (nominal) and the log(1/RD50) was -3.42 mg/m3 air (nominal) (Muller 1984).  

Another study of pentan-1-ol investigated the acute toxicity using an inhalation hazard test (Alarie assay). Mice were exposed via vapour in air. The RD 50 (50% decrease in respiratory rate) was estimated at 2.2 mg/L air (nominal) and the log(1/RD50) was -3.34 mg/m3 air (nominal) (Muller 1984). 

A study with pentan-1-ol was conducted according to ASTM guideline (ASTM (1984) Standard test method for estimating sensory irritancy of airborne chemicals, American Society for Testing and Materials, Philadelphia, Designation: E981-84.) using male CF-1 mice. The animals were exposed head only to the unchanged vapour for 30 min. The RD 50 was estimated at 10.97 mg/L air (nominal) and at 3000 ppm (Hansen 1994).

In addition, several of these studies where the sensory or respiratory tract irritation of mice was investigated after vapour inhalation exposure (Alarie assays) are also discussed in chapter “Irritation. Respiratory tract”.

Taken together, no mortality was observed in acute inhalation toxicity studies conducted with vapours of pentanol, branched and linear or the read-across substances. Only pentanol, branched and linear, (CAS 94624-12-1) was tested as an aerosol, revealing an LC50 value below 14 mg/L in mice, but above 14mg/L in rats and guinea pigs.

 

Dermal route

Acute dermal toxicity of branched and linear pentanols (CAS 94624-12-1) was tested in 4 male New Zealand white rabbits. The animals received a dermal application of approx. 2055, 4078 and 8155 mg/kg bw under occlusive conditions for 24 hours. All animals dosed with 8155 mg/kg bw died within 1 day post dosing. Two of four rabbits dosed with 4078 mg/kg bw died during the dosing period. At the low dose level of 2055 mg/kg bw one rabbit died two days after dosing. At necropsy the following findings were recorded: necrosis and erythema of the exposed skin, hemorrhagic lungs, livers pale and mottled and kidneys pale with pitted surfaces. There was some subcutaneous hemorrhage. Under the conditions of this study, a LD50 of 3662 mg/kg bw was determined (UCC 1955).

Another study with branched and linear pentanols was performed. In this study doses of 200, 500, 794 and 3160 mg/kg bw were applied as an unchanged occlusive path on 4 albino rabbits for 24 h. After dosing, central nervous system depression with labored respiration, ataxia and sprawled limbs were noted and the recovery occurred in 4 to 48 hours after the exposure began. In addition signs of irritation including severe erythema, moderate edema, atonia, blanching, desquamation, necrosis and eschar were observed. Most signs persisted till termination of the 14 day observation period. An LD50 of > 3160 mg/kg bw was determined (Scala & Burtis 1973).

Acute dermal toxicity of the read-across substance 2-methylbutan-1-ol was tested in a study, where 4 male New Zealand White rabbits received a dermal application of approx. 2040 and 4080 mg/kg bw 2-methylbutan-1-ol under occlusive conditions for 24 hours. The testing procedure was comparable to the methods described in OECD TG 402 with one deviation, occlusive instead of semi-occlusive application conditions. There was no mortality in rabbits dosed dermally with 2040 mg/kg bw. At 4080 mg/kg bw all animals died. One rabbit died on the day of test material application and the remaining died on days 1, 3 or 4 after application. Local skin findings included erythema, edema or necrosis of the skin at the application site. No signs of systemic toxicity were recorded. At necropsy, deceased animals showed hemorrhage under the skin, mottled or pale livers and kidneys and lung hemorrhage. The LD50 was determined to be approx. 2889 mg/kg bw (UCC 1959).

For testing the acute dermal toxicity of the read-across substance pentan-1-ol, four male albino rabbits received a dermal application of approx. 1620 and 3240 mg/kg bw and two received an application of approx. 6480 mg/kg bw under occlusive conditions for 24 hours. The testing procedure was comparable to the methods described in OECD TG 402 with one deviation, occlusive instead of semi-occlusive application conditions. At 1620 mg/kg bw no mortality was observed, while all animals at the higher dose levels died. Clinical signs included ataxia and lethargy. At necropsy the following findings were recorded: at 3240 and 6480 mg/kg bw livers with tan mottling, spleens with dark purple mottling and kidneys colored red or brown were observed in animals that died. At 1620 mg/kg bw, livers were mottled dark red. No other gross pathological changes were observed. Since all animals of the 3240 and 6480 mg/kg bw dose groups died within the first 48 hours after application, a LD50 of 2292 mg/kg bw was determined (UCC 1978).

Acute dermal toxicity of the read-across substance 3-methylbutan-1-ol was investigated in a study where four male New Zealand White rabbits received an application of 3-methylbutan-1-ol occluded by an impervious plastic film for 24 hours (Smyth et al.1969). As a result, a LD50 of 3.97 mL/kg bw was reported, which corresponds to approx. 3216 mg/kg bw. No data concerning clinical signs of intoxication or necropsy findings were given.

As a conclusion, the dermal LD50 values are greater than 2000 mg/kg bw for all members of the category. A detailed read-across justification is attached in IUCLID chapter 13. 

 

Other routes

For the read-across substance pentan-1-ol a study assessing the acute toxicity of the test substance applied intraperitoneally was done. Doses of 0.2, 0.4, 0.8 and 1.6 mL/kg bw (corresponding to ca. 163, 326, 652 and 1304 mg/kg bw assuming a density of 0.815 g/mL) were administered to 5 NMRI mice per dose level. Mortality occurred from the 326 mg/kg bw dose group onwards. An LD50 value of ca. 326 mg/kg bw was derived (BASF AG 1973).

In addition an intravenous study with the read-across substance pentan-1-ol was conducted in female white breed H mice. The derived LD50 was 2.09 mmol/kg bw and ca. 184 mg/kg bw (Chvapil 1962). 


Justification for selection of acute toxicity – oral endpoint
Several studies are available (including read-across studies) and were used to evaluate the acute toxicity after oral administration in a weight of evidence approach.

Justification for selection of acute toxicity – inhalation endpoint
Several studies are available and were used to evaluate the acute toxicity after inhalation in a weight of evidence approach.

Justification for selection of acute toxicity – dermal endpoint
Several studies are available and were used to evaluate the acute toxicity after oral administration in a weight of evidence approach.

Justification for classification or non-classification

The available data are considered reliable and suitable for classification purposes under Regulation (EC) No 1272/2008 (CLP).

LD50 values after oral and dermal exposure were above 2000 mg/kg bw. No mortality occurred after exposure for 7 or 8 h to the saturated vapour concentration (approx. 8 – 16 mg/L depending on the substance). Aerosol exposure to the test substance resulted in LC50 values above 14 mg/L for rats and guinea pigs. 7 of 10 mice died at this concentration, but which is well above the upper limit for classification.

Consequently, based on the available data, no classification for acute oral, dermal, or inhalation toxicity is required. Nevertheless, members of the category “pentanols” are legally classified under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 1297/2014, for acute inhalation toxicity category 4 and labeled with H332 (Harmful if inhaled).