N,N-Dimethyl-9-dodecenamide

Endpoint summary

Description of key information

Acute oral toxicity: LD50 (rat) > 2000 mg/kg bw (OECD TG 420)

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:

16 November - 16 December 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9-11 weeks old
- Weight at study initiation: 157 to 190 g
- Fasting period before study: Animals were fasted from the evening of the day prior to dosing to approximately three hours after dosing
- Housing: The animals were housed in groups of up to six in cages that conformed to the 'Code of Practice for the Housing and Care of Animals Bred, Supplied or Used for Scientific
Purposes’ (Home Office, London, 2014). Bedding was provided on a weekly basis to each cage by use of clean European soft wood bedding (Datesand Ltd., Manchester, UK). The bedding had been analysed for specific contaminants and the results retained on file at Labcorp. Each batch of bedding was analysed for specific constituents and contaminants. No contaminants were present in bedding at levels which might have interfered with achieving the objective of the study. Results are retained on file at Labcorp.
- Diet: 5LF2 EU Rodent Diet 14% was freely available to the animals at all times except during the fasting period
- Water: Mains water was provided ad libitum via water bottles
- Acclimation period: 7 to 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Target 19 to 25°C
- Humidity (%): Target 40 - 70 %, below target on two occasions at 21% and 24%,
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16 November 2021 To: 16 December 2021

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL or 200 mg/mL
- Justification for choice of vehicle: The test article was dispersed in corn oil because the test article did not dissolve / suspend in purified water or 1% aqueous methylcellulose.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

300, 2000 mg/kg bw

No. of animals per sex per dose:

300 mg/kg bw - 1 female
2000 mg/kg bw - 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity.
- Body weights: Rats were weighed on Day-1 (day before dosing) and on Days 1, 4, 8 and 15
- Necropsy of survivors performed: yes
- Clinical signs: Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded, at approximately 15 and 30 minutes post-dose, hourly between 1
and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period.

Preliminary study:

The preliminary study was performed using one rat each at doses of 300 and 2000 mg/kg bw. Based on no mortality in the preliminary study a further group of 4 rats were dosed with 2000 mg/kg bw in the main study.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths seen at any dose level

Clinical signs:

other: Hunched posture, laboured breathing, decreased activity and ataxia were noted in one animal treated at 2000 mg/kg. These clinical signs developed from 2 hours after dosing and lasted up to 4 hours after dosing.

Body weight:

other body weight observations

Remarks:

All rats gained weight during the first and second weeks of the observation period

Gross pathology:

No abnormalities were noted at necropsy.

Clinical Signs Following Treatment:

300 mg/kg bw: none

2000 mg/kg bw:

Animal number

Clinical sign

Sign Noted after Dosing on Day 1 (hours)

Sign Noted on Day:

Imm

1/4

1/2

1

2

3

4

2

3

4

5

6

7

8

9 - 15

883

Hunched posture

+

+

+

Dyspnoea

+

Decreased activity

+

+

+

Ataxia

+

+

Key:

Imm Immediately post-dose

+ Sign present (if no entry is made the sign is absent)

Clinical signs	Animal number
	884	885	886	887
No observations	x	x	x	x

Key:

x No clinical signs seen throughout the observation period

Individual Body Weights and Weekly Increments:

Dose     Level (mg/kg)	Animal     Number	Body Weight (g) at:					Increment (g)
		Day -1	Day 1	Day 4	Day 8	Day 15	Day 1 -8	Day 8 -15
300	882	183	170	190	195	203	25	8
2000	883	176	165	176	185	195	20	10
	884	201	190	203	210	216	20	6
	885	165	157	164	171	183	14	12
	886	170	159	175	179	185	20	6
	887	187	172	185	197	209	25	12

Interpretation of results:

Category 5 based on GHS criteria

Executive summary:

This study was conducted to assess the acute toxicity of the test article following a single oral administration to the rat.

In the preliminary study fasted female rats were given the test article as a single dose by oral gavage at dose levels of 300 and 2000 mg/kg. Since there were no deaths in the preliminary study, a further four fasted females were given a single oral dose of test article at a dose level of 2000 mg/kg.

The test article was dispersed in corn oil and administered at a dose volume of 10 mL/kg. All animals were killed on Day 15 and subsequently underwent a full necropsy. There were no deaths. No clinical signs were seen in the animal treated at 300 mg/kg. Hunched posture, laboured breathing, decreased activity and ataxia were noted in one animal treated at 2000 mg/kg. These clinical signs developed from 2 hours after dosing and lasted up to 4 hours after dosing. All rats achieved body weight gains during the first and second weeks of the study. No abnormalities were noted at necropsy.

The test article was classified as Category 5 in respect of its acute oral toxicity according to the Globally Harmonized System of Classification and

Labelling of Chemicals (GHS).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

The acute oral toxicity of the test article in rats was assessed in a study performed according to OECD TG 420.

In the preliminary study fasted female rats were given the test article as a single dose by oral gavage at dose levels of 300 and 2000 mg/kg bw. Since there were no deaths in the preliminary study, a further four fasted females were given a single oral dose of test article at a dose level of 2000 mg/kg.

The test article was dispersed in corn oil and administered at a dose volume of 10 mL/kg. All animals were killed on Day 15 and subsequently underwent a full necropsy. There were no deaths. No clinical signs were seen in the animal treated at 300 mg/kg. Hunched posture, laboured breathing, decreased activity and ataxia were noted in one animal treated at 2000 mg/kg. These clinical signs developed from 2 hours after dosing and lasted up to 4 hours after dosing. All rats achieved body weight gains during the first and second weeks of the study. No abnormalities were noted at necropsy.

The test article was classified as Category 5 in respect of its acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Justification for classification or non-classification

Acute oral toxicity: In a study using females rats performed according to OECD TG 420 the LD50 was > 2000 mg/kg bw. The substance is not classified under CLP.