Nonanamide, N,N-dimethyl-

Endpoint summary

Description of key information

The acute oral toxicity of Genagen PA was investigated according to the Guideline OECD 423. Rats were treated per gavage at dose of up to 2000 mg/kg bw. No effect was observed. The LD50 is found to be higher than 2000 mg/kg bw.

The acute dermal toxicity of Genagen PA was investigated according to the Guideline OECD 403. Rats were treated semi occusively at 2000 mg/kg bw for 24h. No effect was observed. The LD50 is found to be higher than 2000 mg/kg bw:

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:

27 October 2016 to 17 December 2016

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:

Acute Oral Toxicity - Acute Toxic Class Method" adopted on 17 December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and batch No.of test material: 112-2016-11 D
- Expiration date of the batch: May 2018

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Cool and dry (+2 to +8°C)
- Solubility of the test substance in the vehicle: Corn oil (200 mg/mL)

FORM AS APPLIED IN THE TEST: Liquid

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house bred animals
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks
- Weight at study initiation: 167.21 g to 177.61 g
- Fasting period before study: overnight (16 to 18 hours) prior to dosing
- Housing:Three animals were housed in standard polypropylene cage (Size: L 430 x B 285 x H 150 mm)
- Diet (e.g. ad libitum): Teklad Certified (2014SC) Global 14 % Protein Rodent Maintenance Diet (Sterilizable) manufactured by Envigo
- Water (e.g. ad libitum):Deep bore-well water passed through activated charcoal filter and exposed to ultraviolet rays in Aquaguard water filter with purifier
- Acclimation period:Start: 28 October 2016; End: 09 November 2016

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0°C to 22.5°C
- Humidity (%): 50% to 65%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle

IN-LIFE DATES: From: 28 October 2016; To: 24 November 2016

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Step-I & Step-I Confirmation: 30 mg/mL;
Step-II & Step-II Confirmation: 200 mg/mL;
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle:As per the in-house solubility/suspendibility test, test item formed a suspension in corn oil.
- batch no: C-167
- Purity: Pure

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION: A small quantity of vehicle was added to test item and mixed well and thereafter the formulation was transferred into measuring cylinder. Again, a small quantity of vehicle was added to the mortar and rinsed and transferred into the measuring cylinder. Finally the volume was made up to required quantity with vehicle to get a desired volume

CLASS METHOD
- Rationale for the selection of the starting dose: As no information on LD50 of Genagen PA/ N,N-Dimethylnonanamide in rats was available, a starting dose of 300 mg/kg body weight was selected from the fixed dose levels of 5, 50, 300 and 2000 mg/kg body weight

Doses:

Step-I and Step I confirmation: 300 mg/kg body weight;
Step-II and Step II confirmation: 2000 mg/kg body weight

No. of animals per sex per dose:

3 females per step per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily once for clinical signs and weekly body weights
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality at both tested doses (300 and 2000 mg/kg body weight)

Clinical signs:

other: No clinical signs of toxicity observed at both tested doses (300 and 2000 mg/kg body weight)

Gross pathology:

No gross pathological changes were observed in any of the animals at 300 mg/kg body weight in Step I and Step I confirmation and 2000 mg/kg body weight in Step II and Step II confirmation

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity of Genagen PA was investigated according to the Guideline OECD 423. Rats were treated per gavage at dose of up to 2000 mg/kg bw. No effect was observed. The LD50 is found to be higher than 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of Genagen PA was investigated according to the Guideline OECD 423. Rats were treated per gavage at dose of up to 2000 mg/kg bw. No effect was observed. The LD50 is found to be higher than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

One valid Guideline study.

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

Study period:

12 April 2017 to 19 May 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: Genagen PA/ N,N-Dimethylnonanamide

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION [please address all points below]:
- Available GLP studies

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

OECD Guidelines for Testing of Chemicals No. 402 (Section 4: Health Effects) “Acute Dermal Toxicity” adopted on 24 February 1987

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and batch No.of test material: 112-2016-11 D
- Expiration date of the batch: May 2018

STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Cool and dry (+2 to +8°C)

FORM AS APPLIED IN THE TEST
The test item applied topically (dermal exposure) as such

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house bred animals
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 Weeks
- Weight at study initiation: 217.93 g to 231.98 g (males); 201.61 g to 207.91 g (females)
- Housing: Individual in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm)
- Diet (ad libitum): Teklad Certified (2014SC) Global 14 % Protein Rodent Maintenance Diet - Pellet
- Water (e.g. ad libitum):Deep bore-well water passed through activated charcoal filter and exposed to ultraviolet rays in Aquaguard water filter with purifier
- Acclimation period: Start: 13 April 2017; End: 17 April 2017

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4°C to 23.4°C
- Humidity (%): 44% to 64%
- Air changes (per hr): 12 to 15
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle

IN-LIFE DATES: From: 13 April 2017; To: 02 May 2017

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorso-lateral area of the trunk
- % coverage: 10% of the total body surface
- Type of wrap if used: Crepe bandage

REMOVAL OF TEST SUBSTANCE
- Washing: Washed with distilled water and dried with absorbent cotton
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount applied:2000 mg/kg body weight

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs daily once and weekly once weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Not applicable

Preliminary study:

Clinical Signs of Toxicity and Mortality: The animals did not reveal any clinical signs of toxicity and mortality during the observation period and did not reveal any skin reactions.

Body Weight and Percent Change in Body Weight with Respect to Day 1: The body weight and percent change in body weight with respect to Day 1 of all the animals were increased during the observation period.

Pathology: No treatment related gross pathological findings were observed in any of the animals sacrificed at the end of the experimental period.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortalities were noted

Clinical signs:

other: No Clinical signs were noted

Gross pathology:

No gross pathological findings were observed in any of the animals

Other findings:

- Organ weights: Not applicable
- Histopathology: Not applicable
- Potential target organs: Not applicable

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal toxicity of Genagen PA was investigated according to the Guideline OECD 402. Rats were treated semioccusively at dose of 2000 mg/kg bw for 24h. No effect was observed. The LD50 is found to be higher than 2000 mg/kg bw.

Executive summary:

The acute dermal toxicity of Genagen PA was investigated according to the Guideline OECD 402. Rats were treated semioccusively at dose of 2000 mg/kg bw for 24h. No effect was observed. The LD50 is found to be higher than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

One valid Guideline study.

Justification for classification or non-classification

The acute oral toxicity of Genagen PA was investigated according to the Guideline OECD 423. Rats were treated per gavage at dose of up to 2000 mg/kg bw. No effect was observed. The LD50 is found to be higher than 2000 mg/kg bw. No classification is justified for the endpoint acute oral toxicity.

The acute dermal toxicity of Genagen PA was investigated according to the Guideline OECD 403. Rats were treated semi occusively at 2000 mg/kg bw for 24h. No effect was observed. The LD50 is found to be higher than 2000 mg/kg bw. No classification is justified for the endpoint acute oral toxicity.