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

Endpoint summary

Description of key information

Based on the oral and dermal LD50 values, the test substance is considered to have a low acute toxicity potential.


















































  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
    

a moderate acute toxicity potential.

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)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

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

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

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

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).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

ca. 2 000 mg/kg bw

Quality of whole database:

adequate

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no study available

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

other: Acute Dermal Toxicity

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/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
- Weight at study initiation: 241.4 g to 292.9 g
- Fasting period before study: Not applicable
- Housing: Single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad liibitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Approximately 20°C
- Humidity (%): 47% to 57%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: To: 31 July 2012 to 21 August 2012

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 12.6 cm2
- % coverage: 3.3% to 3.6% of body surface
- Type of wrap if used: Semi-occlusive tape ("Micropore") and non-irritating occlusive tape ("Sleek")

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Sterile water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.2 mL/kg
- Constant volume or concentration used: yes

Duration of exposure:

24 hrs

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males, 5 females

Control animals:

not required

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

Statistics:

No

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths occurred at this dose.

Mortality:

There were no unscheduled deaths during the study.

Clinical signs:

other: There were no signs of systemic toxicity and no local findings at the dose sites of any animal at any observation timepoint.

Gross pathology:

Macroscopic findings at necropsy were restricted to dark foci to all lobes of the lungs of one female, Animal No. 7. This finding is commonly observed in rats of this strain and age at these laboratories and is not considered to be related to administration of the substance.

Interpretation of results:

other: CLP criteria not met

Conclusions:

Under the conditions of the study, the dermal LD50 value of the test substance in Sprague-Dawley rats was estimated to be greater than 2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance, in Sprague-Dawley rats according to OECD Guideline 402, in compliance with GLP. A group of ten animals (five males and five females) was given a single, 24 h, occluded dermal application of the test substance to intact skin at a dose level of 2000 mg/kg bw. Animals were observed for signs of reaction to treatment from the day of dosing until the end of the observation period on Day 15. Body weights were recorded weekly and all animals were subjected to a necropsy examination. There were no unscheduled deaths. There were no systemic signs and no local findings at the dose sites noted in any animal at any observation timepoint. Body weight gain was considered to be acceptable for rats of this age and strain. No macroscopic abnormalities attributable to treatment with the substance were recorded at necropsy. Under the conditions of the study, the median lethal dermal dose level (LD50) was determined to be greater than 2000 mg/kg bw (Robertson, 2012).

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Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

experimental result by guideline method under GLP

Additional information

Oral:

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.

Dermal:

A study was conducted to determine the acute dermal toxicity of the test substance, in Sprague-Dawley rats according to OECD Guideline 402, in compliance with GLP. A group of ten animals (five males and five females) was given a single, 24 h, occluded dermal application of the test substance to intact skin at a dose level of 2000 mg/kg bw. Animals were observed for signs of reaction to treatment from the day of dosing until the end of the observation period on Day 15. Body weights were recorded weekly and all animals were subjected to a necropsy examination. There were no unscheduled deaths. There were no systemic signs and no local findings at the dose sites noted in any animal at any observation timepoint. Body weight gain was considered to be acceptable for rats of this age and strain. No macroscopic abnormalities attributable to treatment with the substance were recorded at necropsy. Under the conditions of the study, the median lethal dermal dose level (LD50) was determined to be greater than 2000 mg/kg bw (Robertson, 2012).

Inhalation:

Given the low vapour pressure of the substance (VP = 1.9E-4 Pa at 25°C), which is well below the cut-off of 0.01 Pa as per the ECHA Guidance R.7a, the test substance is considered to have low volatility potential. In case inhalable forms of the substance (either pure or in aqueous solutions) are created under particular conditions (e.g., spraying, elevated temperature/pressure), appropriate risk management measures (due to corrosive nature of the test substance) such as closed systems, exhaust ventilation or wearing of respirators are implemented to control exposure. Under such conditions, the risk to humans following inhalation exposure can be considered minimal and further testing involving vertebrate animals may be omitted, in accordance with Annex XI (1.2) of the REACH regulation.

Justification for classification or non-classification

Based on the results from the acute oral and dermal studies, the test substance warrants an ‘Acute Tox. 4; H302: harmful if swallowed’ classification for oral route and no classification for the dermal route according to EU CLP (EC 1272/2008) criteria.