Hexanamide, N-(2-hydroxyethyl)-3,5,5-trimethyl-

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-hydroxyethyl)-3,5,5-trimethylhexanamide

EC Number:

800-884-5

Cas Number:

1154308-86-7

Molecular formula:

C11 H23 N1 O2

IUPAC Name:

N-(2-hydroxyethyl)-3,5,5-trimethylhexanamide

Test material form:

other: liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Margate
- Age at study initiation: 8 to 10 weeks
- Fasting period before study: Overnight on the day before dosing
- Housing: 3 per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 21°C
- Humidity (%): 46% to 59%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: To: 17 July 2012 to 11 September 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.2 mL/kg

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Acute Toxicity on Sponsor's Safety Data Sheet stated that the oral LD50 in rats is >5000 mg/kg
The test item was administered as supplied (ie not formulated in a vehicle)

MAXIMUM DOSE VOLUME APPLIED: 2.2 mL/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The Acute Toxicity Data section of the Sponsor's Safety Data Sheet stated that the acute oral LD50 in rats is >5000 mg/kg

Doses:

300 mg/kg and 2000 mg/kg

No. of animals per sex per dose:

6 at 300 mg/kg and 6 at 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations at least 5 times on the day of dosing, then daily for 14 days. Body weights on Days 1, 8 and 15
- Necropsy of survivors performed: yes (also decedents)
- Other examinations performed: none

Statistics:

None

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Two of 6 animals given 2000 mg/kg bw were euthanized during the study.

Mortality:

Two of the 6 animals that were treated with the substance at a dose level of 2000 mg/kg (Group 2 Animal Nos. 6 and 4) were euthanised at approximately 3½ h and 5¾ h post dose, respectively, because of the severity of their clinical signs.
There were no deaths among the Group 1 animals treated with the substance at a dose level of 2000 mg/kg or among the 6 animals that received the 300 mg/kg dose level (Groups 3 and 4).

Clinical signs:

other: All 6 animals treated at 2000 mg/kg displayed subdued behaviour and rolling gait within approximately 15 min of dosing and all were prostrate within approximately 30 min. Five of these animals displayed hunched posture, piloerection and staggering and 5

Gross pathology:

Necropsy revealed no macroscopic abnormalities in any animal.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

other: Category 4 based on CLP criteria

Conclusions:

Under the conditions of the study, the oral LD50 value was considered to be 2000 mg/kg bw, indicating low acute oral toxicity potential.

Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance, in Sprague-Dawley rats according to OECD Guideline 423, in compliance with GLP. Two groups of six fasted females were treated with the test substance at a dose level of and 2000 (Group 1 and 2) and 300 mg/kg bw (Group 3 and 4). The animals were observed for up to 14 days after the day of dosing. The following parameters and end points were evaluated in this study: clinical signs, body weights, body weight changes, and gross necropsy findings. Two of the 6 animals that were treated with the substance at a dose level of 2000 mg//kg bw (Group 2) bw were euthanised at approximately 3½ h and 5¾ h post dose, respectively, because of the severity of their clinical signs. Signs were noted in these animals from 5 min post dose and at time of euthanasia included respiratory difficulties, unresponsiveness, watery discharge from the eyes and coldness to the touch. All 6 animals treated at 2000 mg/kg bw displayed subdued behaviour and rolling gait and were prostrate within approximately 30 min of dosing. Other signs noted in Day 1 included hunched posture, piloerection, staggering and slow and irregular respiration. Lowered body posture was recorded in all of these animals during the first 2 days of the observation period. Among surviving animals, the majority of these signs had resolved by Day 2 and all had resolved by Day 3. In animals treated at 300 mg/kg bw the clinical signs on Day 1 included subdued behaviour, hunched posture, staggering, piloerection and partial eye closure. All signs had resolved by Day 2. The body weight gains of animals treated at 300 mg/kg bw were considered to be acceptable for rats of this age and strain. Lower body weight gains were recorded in surviving animals treated at 2000 mg/kg bw. No macroscopic abnormalities were recorded in any of the animals at necropsy. Under the conditions of the study, the oral LD50 value was considered to be 2000 mg/kg bw (Robertson, 2012).