Isotridecan-1-ol

Endpoint summary

Description of key information

- acute oral:
rat (male/female): LD50 > 2000 mg/kg bw (BASF, 2002)
rat (male): LD50 = 17.2 ml/kg bw (ca. 14500 mg/kg bw; Smyth, H.F. et al., 1962)

mouse (m/f): LD50 > 5395 mg/kg (BASF, 1963)
- acute inhalation:
rat (male/female), IRT: LC0 >/= 0.3 mg/l (BASF, 1963)
rat, IRT: LC0 >/= 0.0064 mg/l (Smyth, H.F. et al., 1962)

rat, IRT: LC0 >=0.006mg/l (calculated sat. vapor conc., Scala, 1973)
- acute dermal:
rabbits (male): LD50 = 7.07 ml/kg bw (ca. 5960 mg/kg bw; Smyth, H.F. et al., 1962)
rabbits: LD50 > 2600 mg/kg bw (Scala, R.A. and Burtis, E.G., 1973)

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(adopted March 22, 1996)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld, Germany
- Age at study initiation: Young adult animals (male animals approx. 8 - 12 weeks, female animals approx. 14 - 18 weeks)
- Weight at study initiation: mean(males): 221 g; mean(females): 211 g
- Fasting period before study: yes (Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.)
- Housing: Single housing
- Diet: Provimi Kliba SA, Kaiseraugst, Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: Acclimatization for at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

other: olive oil Ph.Eur./DAB

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40 g/100 ml
- Justification for choice of vehicle: Inhomogeneous in aqueous formulation, solution in olive oil Ph.Eur/DAB.

MAXIMUM DOSE VOLUME APPLIED: 5 ml /kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and its composition, no pronounced acute oral toxicity was expected. Therefore, a starting dose of 2000 mg/kg body weight (limit test) has been chosen in the first step with 3 female animals. As none of those animals died, 2000 mg/kg body weight were administered to 3 male animals in a second step. Because no mortality occurred either the study fulfilled the criteria for a limit test and was terminated.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 male and 3 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: at least 14 days
- Frequency of observations and weighing:
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study.
Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals;
Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes (Necropsy with gross-pathology examination on the last day of the observation period after killing with C02.)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Male animal symptoms: Sign of toxicity noted in the 2000 mg/kg administration group was piloerection and was observed on hour 5 after administration. Female animal symptoms: No signs of toxicity were observed during clinical examination in the 2000 mg/kg

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (3 males and 3 females) examined at termination of the study.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 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:

weight of evidence

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:

The test was performed in principle as described in OECD test guideline 403. It demonstrates the toxicity of an atmosphere saturated with vapors of the volatile components of a test substance at 20°C. Young adult laboratory rats, 6 per sex, were exposed sequentially to the vapors generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h. The exposure was subsequently repeated in the same manner. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as quotient of the amount of test substance weight loss during exposure, and the amount of air used during exposure. Group-wise documentation of clinical signs was performed over a 7 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period.

GLP compliance:

no

Test type:

other: inhalation risk test

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Diet: ad libitum
- Water: ad libitum

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Source and rate of air: No source mentioned; 200 L/h

TEST ATMOSPHERE
- Brief description of analytical method used: no analytics performed
- Samples taken from breathing zone: no

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

No verification of the concentration was performed. Nominal concentration: 0.3 mg/l (determined by means of re-weighing)

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: group wise documentation on working days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 0.3 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

8 h

Remarks on result:

other: IRT: the calculated nominal test atmosphere has to be considered as saturated at 20°C

Mortality:

There was no mortality after 8 h exposure of a saturated atmosphere.

Clinical signs:

other: No clinical findings were noted.

Body weight:

no data

Gross pathology:

No gross pathological findings were noted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

0 mg/m³ air

Quality of whole database:

no mortality at saturated vapour concentration in three studies

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

The LD50 was determined by a method closely akin to the one-day cuff method of Draize et al. (1944) using groups of 4 male albino New Zealand rabbits. The fur was removed by clipping and the dose was retained beneath an impervious plastic film (i.e. occlusive). The animals were immobilized/exposed for 24 hours. Afterwards, the film was removed and the animals were observed for 14 days.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 - 3.5 kg

Type of coverage:

occlusive

Vehicle:

not specified

Duration of exposure:

24 h

Doses:

no data

No. of animals per sex per dose:

4 male animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Statistics:

LD50 value and its confidence interval was estimated by the method of Thompson (1947) using the tables of Weil (1952).

Sex:

male

Dose descriptor:

LD50

Effect level:

7.07 mL/kg bw

Based on:

test mat.

Remarks on result:

other: (confidence intervals: 2.33 - 21.4 ml/kg bw; = ca. 5960 mg/kg bw, confidence interval: 1964 - 18040 mg/kg bw, calculated by the density of 843 g/l)

Mortality:

no data

Clinical signs:

other: no data

Gross pathology:

no data

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 960 mg/kg bw

Additional information

Oral:

Acute oral toxicity was evaluated in a reliable GLP-study conducted according to OECD 423. Three male and three female Wistar rats received doses of 2000 mg/kg bw of iso-tridecan-1 -ol in olive oil Ph.Eur./DAB (BASF, 2002). No mortality occurred during the observation period of at least 14 days. 5 hours after administration piloerection was observed in the male animals. No clinical signs were observed in the female animals. Under the conditions of this study the median lethal dose was found to be greater than 2000 mg/kg body weight for male and female rats.

In a reliable publication of Smyth, H.F. et al (1962) the single oral toxicity of the test substance was determined by gastric intubation of groups of 5 non-fastened, male Carworth Wistar rats. The LD50 was determined as 17.2 ml/kg bw (ca. 14500 mg/kg bw).

In a publication by Scala & Burtis (1973), the LD 50 for Tridecanol was estimated as 4750 mg/kg in male rats. Except for the LD50 value, no data on mortality was reported, but the authors state that the mortality pattern did not allow derivation of a reliable LD50 value. Even so, the data support the low oral toxicity observed in the remaining studies.

In an old study by BASF (1963), five mice per sex and group were treated from 169 mg/kg to 5395mg/kg. Symptoms on the day of exposure included reduced activity and intermittant respiration without clear dose dependency. There were no symptoms on the following days or during necropsy. One mouse in the high dose group died after 5 days without clinical symptoms. The LD50 was thus above 5395mg/kg.

Data on the three structurally similar alcohols also show low toxicity of this group of substances:

CAS 10042 -59 -8 (Propylheptanol): LD 50 = 5400 mg/kg (rat)

CAS 27458 -94 -2 (Isononanol): LD 50 = 3950 mg/kg (rat)

CAS 25339 -17 -7 (Isodecanol): LD50 = app. 4600mg/kg (mouse)

Inhalation:

 

Data of the acute inhalation toxicity of CAS 27458 -92 -0 are restricted to inhalation hazard tests.

6 male and 6 female Wistar rats were exposed (nose/head only) to a saturated test substance atmosphere of 0.3 mg/L (nominal) for 8 h (BASF, 1963). The observation period lasted 7 days. No mortality or clinical signs were observed. The test was performed in principle as described in OECD test guideline 403, but it was conducted before the implementation of GLP and OECD Guidelines. It should be noted that the concentration was determined by weighing of the test substance prior and after the exposure. The calculated saturated vapour concentration is 0.006mg/L, which means that (more likely) test substance adhered to the testing apparatus and was lost for the experiment, resulting in a lower exposure concentration, or that a mixture of vapour and aerosol was tested.

In an Inhalation Risk Test performed by Smyth, H.F. et al. (1962) concentrated vapor was inhaled by groups of 6 male or female albino rats. The temperature at vapor generation was room temperature. Vapor saturation at 20°C is 0.0064 mg/l (vapor pressure (20°C): 0.00078 hPa). Inhalations were continued for 8 hours. The observation period lasted 14 days. After the 8 hour-exposure no mortality occurred. No information on clinical signs was given.

In a third IRT by Scala & Burtis (1973), all rats, mice, and guinea pigs (10 per species) survived inhalation of the saturated vapour for 6 hours. Only slight signs of local irritation were noted. All animals appeared normal within 1h after exposure. No effects were noted during necropsy. Thus the LC50 is above the saturated vapour concentration for these three species, calculated as 0.0063mg/L, based on the moleculare weight of Tridecanol.

Data on the three structurally similar alcohols also show no mortality at saturated vapour concentration. Additionally, in a study equivalent to OECD 403, an LC50 value for Isononanol (CAS 27458 -94 -2) above 21.7 mg/L was determined for mice, rats, and guinea pigs.

Dermal:

 

Acute dermal toxicity was determined by a method closely akin to the one-day cuff method of Draize et al. (1944) using groups of 4 male albino rabbits (Smyth, H.F. et al, 1962). The fur was removed by clipping and the dose was retained beneath an impervious plastic film (i.e. occlusive). The animals were immobilized/exposed for 24 hours. Afterwards, the film was removed and the animals were observed for 14 days. An LD50 value of 7.07 ml/kg bw (ca. 5960 mg/kg bw) was established. No information on clinical signs was given.

In the publication of Scala, R.A. and Burtis, E.G. (1973) tridecanol was applied full-strength to the closely clipped, intact abdominal skin of albino rabbits in groups of four. The exposed area was covered with an occlusive binding of dental damming for 24 hours. After the exposure, the binding was removed, and the remaining material was cleaned from the skin. The observation period was 7 days and a LD50 of > 2600 mg/kg bw was established. No mortality and signs of toxicity were observed, but moderate irritation could be seen.

Data on the three structurally similar alcohols also show low toxicity of this group of substances:

CAS 10042 -59 -8 (Propylheptanol): LD 50 > 5010 mg/kg (rabbit)

CAS 27458 -94 -2 (Isononanol): LD 50 > 4000 mg/kg (rat)

CAS 25339 -17 -7 (Isodecanol): LD50 > 2600 mg/kg (rabbit)

Justification for classification or non-classification

Concerning acute toxicity, the available data is conclusive. No classification according to 1272/2008/EC (CLP) criteria is required.