1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. residues

Endpoint summary

Description of key information

The LD50/LC50 values derived from the key limit studies in male and female rats were >5000 mg/kg bw and >5400 mg/m³ for oral and inhalation exposure, respectively.

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:

1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

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: Interfauna U.K. Limited, Wyton, Huntingdon, U.K.
- Age at study initiation: 5-8 weeks old
- Weight at study initiation: 120-127 g (males), 135-150 g (females)
- Fasting period: food was removed at day -1 and then redistributed 2 hours after treatment
- Housing: polypropylene cages with sawdust bedding
- Diet: Rat and Mouse Expanded Diet No. 1 (Special Diets Services Ltd., Witham, Essex, U.K.), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 50-65 %
- Air changes: approximately 10 changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: From: 18-Sep-1985 To: 08-Oct-1985

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The animals received a dose of 5000 mg/kg bw of the test item administered by gavage (dose volume: 5.62 mL/kg bw) using a metal cannula attached to a graduated syringe. The dose level for each animal was calculated according to its body weight at the time of dosing.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs were recorded 1 and 4 hours after dosing and then once daily for 14 days, body weight was measured on days 0 (day of treatment), 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic observation

Preliminary study:

No mortality was noted 5 days after dosing. The oral LD50 of the test item was considered to be >5000 mg/kg bw. This dose level was used for the main study.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

There was no mortality.

Clinical signs:

other: Hunched posture and piloerection were observed in all treated animals 1 hour after dosing. Other signs of overt toxicity seen in some animals only at this time consisted of lethargy, ataxia and a decreased respiratory rate. All males and one female contin

Gross pathology:

There were no macroscopic abnormalities.

Interpretation of results:

other: slightly toxic

Executive summary:

In an acute oral toxicity study (Jones & Collier, 1985), a group of fasted young adult Sprague-Dawley rats (5 males, 5 females) were given a single dose of ZD 8 Gewaschen by oral gavage at a dose level of 5000 mg/kg bw and observed for 14 days. There was no mortality or other relevant findings. The oral LD50 (males and females) was >5000 mg/kg bw.

ZD 8 Gewaschen is of low toxicity based on the LD50 in male and female rats.

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:

2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories Ltd., Kreuzelweg 53, 5961 NM Horst / Netherlands
- Age at study initiation: 10 weeks old (males), 11 weeks old (females)
- Weight at study initiation: 275.4-310.7 g (males), 195.3-215.4 g (females)
- Housing: in groups of five (same sex) in Makrolon type-IV cages
- Diet: Kliba-Nafag 3433 rat maintenance diet (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland), ad libitum, except during exposure
- Water: community tap water, ad libitum
- Acclimation period: 14 days (performed under Harlan Laboratories Study B68308)

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30-70 %
- Air changes: 10-15/hour
- Photoperiod: 12 hours dark/12 hours light

IN-LIFE DATES: From: 23-Sep-2009 To: 07-Oct-2009

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: animals were confined separately in restraint tubes which were positioned radially around the flow-past, nose-only exposure chamber.
- Method of holding animals in test chamber: restraint tubes
- Rate of air: 1.0 L/min
- System of generating particulates/aerosols: nebulizer with test item reservoir (Hospitak no. 950 with stainless steel injector)
- Method of particle size determination: gravimetrically, using a 7-stage cascade Mercer impactor (Model 02-130. In-Tox. Products Inc., Albuquerque, New Mexico, U.S.A.)
- Oxygen concentration, temperature and humidity in air chamber (n = 9): mean oxygen concentration: 20.6 ± 0.1 %, mean temperature: 23.1 ± 0.2 °C, mean relative humidity: 4.0 ± 1.02

TEST ATMOSPHERE
- Brief description of analytical method used: aerosol concentrations were determined gravimetrically using Millipore durapore filters (type HVLP). The filters were weighed before and immediately after sampling. The test aerosol concentration was calculated from the amount of test item determined by gravimetry and the sample volume. The particle size distribution was measured using a 7-stage cascade Mercer impactor. Mass median aerodynamic diameters and geometric standard deviations were calculated on the basis of the results from the impactor.
- Samples taken from breathing zone: Yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.39-1.40 µm (n = 3) / 1.95-1.97 (n = 3)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

from the analytical data and the volume of the inhalation atmosphere sample, the concentrations were calculated in mg/L.

Duration of exposure:

4 h

Concentrations:

5.4 ± 0.1 mg/L (n = 4)

No. of animals per sex per dose:

5 animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were examined for clinical signs five times on day 1 and daily thereafter; body weight was recorded on days 1 (before exposure), 4, 8 and 15.
- Necropsy of survivors performed: on day 15
- Other examinations performed: macroscopic examination

Statistics:

No statistical analysis was performed as only one group was allocated to the study.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.4 mg/L air

Exp. duration:

4 h

Remarks on result:

other: None

Mortality:

There was no mortality.

Clinical signs:

other: All animals showed a slightly decreased spontaneous activity and moderately ruffled fur immediately after exposure and one hour afterwards. Slightly ruffled fur was still present in all animals up to test day 4 and for two further days in some animals. Ad

Body weight:

From day 1 to day 4, body weight loss (up to 7 %) or stagnation of body weight was noted in all animals. This observation was considered to be mainly related to treatment with the test item due to the incidence and the duration of the effect in some animals. However, the restraint procedure is likely to have added to the observed effect. Thereafter, all animals showed elevated body weights on day 15 as compared to the body weights on day 1.

Gross pathology:

There were no macroscopic findings at necropsy.

Interpretation of results:

other: slightly toxic

Executive summary:

In an acute inhalation toxicity study (Schuler, 2010), a group of young adult Wistar rats (5 males, 5 females) were exposed by inhalation route (nose only) to an aerosol generated from undiluted Montanol 800 (>98 %, MMAD 1.39 -1.40 µm) for 4 hours at a single concentration of 5.4 mg/L. Animals then were observed for 14 days. No animal died and all gained body weight. The transient clinical findings noted during the observation period were confined to decreased activity, ruffled fur and red secretions from the nose. The LC50 was >5.4 mg/L after 4 hours.

Montanol 800 is classified as being of low toxicity based on the LC50 in males and females.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 400 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues has a low acute toxicity by the oral and inhalation route of exposure.

In an acute oral toxicity study (Jones & Collier, 1985), a group of fasted young adult Sprague-Dawley rats (5 males, 5 females) were given a single dose of ZD 8 Gewaschen (identical to 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues) by oral gavage at a dose level of 5000 mg/kg bw and observed for 14 days. There was no mortality or other relevant findings. The oral LD50 (males and females) was >5000 mg/kg bw. This finding was supported by an acute oral toxicity study (Richeux, 2008) in which a group of fasted young adult Sprague-Dawley rats (6 females) was given a single dose of Zorgol 8 (identical to 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues) by oral gavage at a dose level of 2000 mg/kg bw and observed for 14 days. There was no mortality or other relevant findings. The oral LD50 (females) was >2000 mg/kg bw and was considered to be >5000 mg/kg bw.

In an acute inhalation toxicity study (Schuler, 2010), a group of young adult Wistar rats (5 males, 5 females) were exposed by inhalation route (nose only) to an aerosol generated from undiluted 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues (>98 %, MMAD 1.39 -1.40 µm) for 4 hours at a single concentration of 5.4 mg/L (5400 mg/m³). Animals then were observed for 14 days. No animal died and all gained body weight. The transient clinical findings noted during the observation period were confined to decreased activity, ruffled fur and red secretions from the nose. The LC50 was >5400 mg/m³ after 4 hours.

Justification for selection of acute toxicity – oral endpoint
Guideline study according to GLP

Justification for selection of acute toxicity – inhalation endpoint
Guideline study according to GLP

Justification for classification or non-classification

Based on the results of the acute oral and inhalation key toxicity studies, 1-Hexanol, 2-ethyl-, manuf. of, by-products from, distn. Residues is not subject to classification and labelling for acute toxic effects according to Directive 67/548/EEC and Regulation 1272/2008/EC.