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 pentan-1-ol or the read-across substances were applied as vapour. In a study conducted on a read-across substance 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
3 645 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.
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
2 292 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 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, 5184 mg/kg bw 3/10, 2/10, 8/10 and 9/10 animals were found dead within 24 hrs, respectively. 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. 

 

A further study is available which was conducted with pentan-1-ol. Male Wistar rats were administered with approx. 3258, 6515 and 13030 mg/kg bw pentan-1-ol by gavage (Carnegie-Mellon Institute, Union Carbide Corp. 1978). 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.

 

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.

 

Acute oral toxicity of a second read across substance, 2-methyl-1-butanol, was also evaluated following the same procedure (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 corneal reflex absent, piloerection, 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.

 

Acute oral toxicity of the last category member and read across substance “branched and linear pentanols” (CAS 94624-12-1) was evaluated in a study, where 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 (Scala & Burtis 1973). 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.

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

 

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

 

 

Inhalation route

Acute inhalative toxicity to 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.

 

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 (Carnegie-Mellon Institute, Union Carbide Corp. 1978).

 

Acute inhalative toxicity of 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.

 

An inhalation hazard test (IHT) according to the method described in the Annex of OECD TG 403 (1981) was also conducted to assess the acute inhalative toxicity to 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.

 

An Inhalation hazard Test is also available for branched and linear pentanols (CAS 94624-12-1) (Union Carbide Corp., 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 in exposure. All rats were active a few seconds after cessation of the exposure.

 

For pentan-1-ol no animal studies including inhalation exposure to an aerosol are available, but valid aerosol studies in rats, mice and guinea pigs conducted with an isomer mixture equivalent to pentanol, branched and linear (CAS No. 94624-12-1) are taken into consideration by read-across.

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.

 

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

 

Taken together, no mortality was observed in acute inhalation toxicity studies conducted with vapours of pentan-1-ol or the read across substances. Only one category member (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

For testing the acute dermal toxicity of 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.

 

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.

 

Acute dermal toxicity of 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.

 

Additionally, for testing branched and linear pentanols (CAS 94624-12-1), 4 male New Zealand white rabbits 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.

 

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

 

 

Other routes

As an additional information a study report is available on a study assessing the acute toxicity of the test substance applied intraperitoneally. Doses of 0.2, 0.4, 0.8, 1.6 mL/kg bw (corresponding to ca. 163, 326, 652, 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.

 


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 dermal 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 2000mg/kg. No mortality occured after exposure for 7 or 8h to the saturated vapour concentration (app. 8 - 16mg/L depending on the substance). Aerosol exposure to the read across substance CAS 94624 -12 -1 resulted in LC50 values above 14mg/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, Pentanol is 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).