Registration Dossier

Administrative data

Description of key information

skin:
The test substance was considered to be irritating to the skin.
eyes:
The test substance was found to cause irreversible damage to the eyes.
respiratory tract:
The test substance was found to cause repiratory irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

Pentan-1-ol was tested in vivo for skin irritation (BASF AG 1973). 0.5 mL of pentan-1-ol was applied to the intact skin of one male and one female Vienna White rabbit under occlusion for 1, 5 and 15 min as well as for 20 hours. The scores for erythema and edema after 1, 5, and 15 minutes application were calculated as 0.3 and 0, 1 and 0, 1.3 and 0, respectively. Scaling was still persistent at the end of the 8 day observation period after the 15 minutes, but all other findings were reversible. No reliable edema and erythema values could be obtained for the 20 hour application, because necrosis in one and severe scaling in the other animal made scoring impossible.

In another study, a 4 hour occlusive application led to necrosis in 2 of 4 rabbits, while after 24 hours unoccluded application no irritation was noted (Carnegie-Mellon Institute 1978).

3-methylbutan-1-ol was investigated for its skin irritating property in a study which was performed according to Guideline Federal Register 38, No. 187, § 1500.41 (Draize test, BASF AG 1979a). 0.5 mL of 3-methylbutan-1-ol was applied to the intact skin of five male and one female Vienna White rabbit under occlusion for 24 hours. Two additional animals each were exposed for 5 minutes as well as for 2 hours. A five minute exposure did not lead to skin irritation. Mean erythema and edema values were 1.3 and 1.7 respectively after 2 h application. Crust formation was additionally observed, but the skin underneath was intact. Occluded exposure for 24 hours led to necrosis in three of the six animals and desquamation in the others. Erythema and edema scores were 2.4 and 2.1, respectively. Since necrosis was only observed under harsh condition, i.e., 24h occlusive exposure, but not after 2h, the substance is considered to be irritant to the skin.

Following the same procedure, 2-methyl-1-butanol was tested: A study was conducted according to guideline Federal Register 38, No 187, § 1500.41 (Draize test, BASF AG 1979b), where 0.5 mL of 2-methyl-1-butanol was applied to the intact skin of five male and one female Vienna White rabbits under occlusion for 24 hours. Two additional animals each were exposed for 5 minutes as well as for 2 hours. The scores for erythema and edema after the 5 minute, 2 and 24 hours application were calculated as 1.2 and 0, 2.5 and 2.8, 2.4 and 2.1, respectively. Slight necrosis and scaling was persistent at the end of 8 day observation period after the 24 hours applications in three of the six animals.

In an acute dermal toxicity study with the same substance, only minimal irritation occurred in 2 of 5 rabbits after 24 hours uncovered exposure (Union Carbide 1959).

It has to be taken into account that testing under occlusive conditions has to be regarded as over-predictive, and the test results should be considered with caution. Skin necrosis was only observed when tested under occlusive conditions for at least 4 hours, while no necrosis was noted at shorter exposure times. Additionally, open application of the test components for 24h caused hardly any skin irritation.

Additionally, skin irritation by pentan-1-ol was also evaluated in studies 30 human volunteers (please refer to IUCLID5, section 7.10.5). In this study, 0.2 mL of pentan-1 -ol were applied on a 25 mm plain Hill Top Chamber containing a Webril pad to the skin of the upper outer arm (Basketter et al. 2004). After an application of 15 and 30 minutes through 1, 2, 3 and 4 hours, pentan-1 -ol was found to be not irritating to skin.

Taking all the presented animal and human evidence into account, the substance is not necessarily skin irritating according to the criteria of Regulation (EC) No 1272/2008 (GHS EU). Nevertheless, the substance is classified according to Annex VI of Regulation (EC) No 1272/2008 as skin irritant category 2. This classification according to GHS (EU) shall be retained in order to ensure the safety of workers and general population.  

 

Eye irritation:

0.05 mL of undiluted pentan-1-ol were instilled into the conjunctival sac of the right eye while the left eye served as control (BASF AG 1973). As a result the scores for corneal opacity, iris, conjunctival erythema and chemosis were determined to be 2.7, 0.8, 1.5 and 1.5, respectively. In addition, ulceration was observed in the treated eyes of both animals until the end of the observation period. The observed effects were not reversible within the observation period of 8 days; scores for iritis even increased over time. In a non-guideline study, 0.005mL pentan-1-ol were instilled into the eyes of 5 rabbits (Carnegie-Mellon Institute 1978). The eyes were scored once after 24 hours. Moderate to severe corneal injury and iritis were noted in 2 animals. 0.5mL of a 15% solution resulted in the same effects in 2 out of 4 rabbits. No corneal injury was induced by a 0.5mL of a 5% solution. Joller et al. (1994) reported that the effects on the rabbit’s eye observed with Pentan-1-ol in an OECD 405 study were not reversible after 14 days. The overall irritation score was 28. No further details on effects or single animal data were provided. In an in vitro study similar to OECD 437, VanParys et al. (1993) treated six bovine corneas for 10 minutes with Pentan-1-ol. They obtained an overall irritation score (IVIS) of 77.4 – 94, calculated from corneal opacity values of 4.35 – 5.28 and optical densities of 11.1 – 15.9. Substances with IVIS scores above 55 are considered corrosive to the eye. 3-methylbutan-1-ol was tested for its irritating property to eyes in a study performed according to the guideline Federal Register 38, No 187, § 1500.41 (BASF AG 1979a). 0.1 mL of pure 3-methylbutan-1-ol was instilled into the conjunctival sac of the right eye of six Vienna White rabbits. The eyes were not washed out after 24 hours. As a result the scores for corneal opacity, iris, conjunctival erythema and chemosis were found to be 1.1, 0.3, 2.8 and 1.1, respectively. At the end of the observation period corneal opacity and chemosis was still apparent. In addition, ulceration in one animal was observed. Based on these results, the substance needs to be considered corrosive to the eyes, even though the results might be over-predictive due to the observation period of only eight days in contrast to 21 days as specified in the OECD guideline. Following the same procedure, 2-methylbutan-1-ol was tested (BASF AG 1979b): 0.1 mL of undiluted 2-methyl-1-butanol was instilled into the conjunctival sac of the right eye of six Vienna White rabbits. As a result the scores for corneal opacity, iris, conjunctival erythema and chemosis were determined to be 1, 1, 1.9 and 1.2, respectively. Corneal opacity was persistent in 5/6 animals at the end of the observation period of 8 days, as was iritis in one and conjunctival redness in all animals. Though there was a decrease in the severity of the reactions, scars were seen in three rabbits, and it cannot be proven without doubt that the effects would have been reversible within 21 days, if the observation period would have been extended to match the current guideline. In a non-guideline study, 0.005mL 2-methylbutan-1-ol were instilled into the eyes of an unspecified number of rabbits (Union Carbide 1959). The eyes were scored once after 24 hours. Severe corneal necrosis was noted. 0.5mL of a 15% solution in propylene glycol resulted in the same effects. No corneal injury was induced by a 0.5mL of a 5% solution.

 

Respiratory irritation:

Several Alarie assays were conducted with pentan-1-ol in mice in order to determine the potency of the substance to cause sensory irritation (please refer to IUCLID5, section 7.2.2). Sensory irritation was evaluated in CF-1 male mice via measurement of changes in respiratory rate during a 30 minute exposure. The concentration which caused a 50 % decrease in respiratory rate represents the RD50. After 30 min exposure, the RD50 was approx. 10.97 mg/L (Hansen & Nielsen 1994). In another study, an RD50 of approx. 14.8 mg/L was determined in Swiss Webster mice after 10 min exposure to test substance vapours (Kane et al. 1980). Based on the vapour pressure of 2.04 hPa at 20°C and the molecular weight of 88.15 g/mol, the saturated vapour concentration was calculated to be 7.41 mg/L. Therefore, under the conditions of the study the animals might have been exposed at 14.8 mg/L to a vapour-aerosol mixture. Muller & Greff (1984) reported an RD50 of 2.2 mg/L in mice (strain unknown) after exposure to pentan-1-ol vapours (duration unknown).

 

Two Alarie assays were conducted with 3-methylbutan-1-ol in mice in order to determine the potency of the substance to cause sensory irritation. Sensory irritation was evaluated in mice via measurement of changes in respiratory rate during exposure to test substance vapours. After 10 min exposure to test substance vapours, an RD50 of approx. 16.28 mg/L was determined in Swiss Webster mice (Kane et al. 1980). Based on the vapour pressure of 3.0 hPa at 20°C and the molecular weight of 88.15 g/mol, the saturated vapour concentration was calculated to be 10.90 mg/L. Therefore, under the conditions of the study the animals might have been exposed to a vapour-aerosol mixture. Muller & Greff (1984) reported an RD50 of 2.63 mg/L in mice (strain unknown) after exposure to 3-methylbutan-1-ol vapours (duration unknown).

 

In human subjects (please refer to IUCLID5, section 7.10.5), the pungency detection threshold of pentan-1-ol was found to be 1603 ppm equivalent to 5.86 mg/L (Cometto-Muniz & Cain 1990).

 

Short-term exposure to an aerosol of the read across substance branched and linear pentanols (CAS No. 94624-12-1) at approx. 14 mg/L air for 6 hours caused irritation of mucous membranes of the eyes, nose, throat and respiratory passage in rats, rabbits and guinea pigs (Scala & Burtis 1973).

 

The presented experimental data from human and animal studies conducted with pentan-1-ol and its structural analogue 3-methylbutan-1-ol endorse the classification of pentan-1-ol as respiratory tract irritant according to Annex VI of Regulation (EC) No 1272/2008. A detailled read across justification is attached in IUCLID chapter 13. 

 

 

 


Justification for selection of skin irritation / corrosion endpoint:
Several reliable studies were used for evaluation of the skin irritating property of the test substance in a weight of evidence approach.

Justification for selection of eye irritation endpoint:
Several reliable studies were used for evaluation of the eye irritating property of the test substance in a weight of evidence approach.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

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

As a result, the substance is considered to be classified for skin irritation into category 2 and eye damage category 1 under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 1297/2014.

Due to its respiratory irritating property the substance is also classified for specific target organ toxicity after single exposure (STOT SE) into category 3 and labeled with H335: May cause respiratory irritation under Regulation (EC) No 1272/2008, as amended for the seventh time in Regulation (EC) No 1297/2014.