N,N-Diethylacrylamide

Endpoint summary

Description of key information

Acute oral:

The LD50 to rats of test item was estimated to be 739 mg/kg bodyweight.

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:

From 1993-05-18 to 1993-06-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Batch No.: not specified
Purity: not specified

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Ltd., Bicester, Oxon, England
- Age at study initiation: approximately four to seven weeks of age
- Weight at study initiation: 112 to 158g
- Housing: be housed in groups of up to five rats of the same sex in metal cages with wire floors
- Diet: Biosure LAD
- Water: Anglian water
- Acclimation period: a minimun period of seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 21
- Humidity (%): 58
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial light in each 24 hours period

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

Test substance preparation: the test item was administered at a volume not exceeding 0.87mL/kg in the main study. The absorption of the test itme was not determined.

Doses:

500, 640 and 800 mg/kg bodyweight

No. of animals per sex per dose:

five male and five females per dosage

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs: day 1, 5 and 14 after dosing. body weight: day 1, 8 and 15 or death
- Necropsy of survivors performed: yes

Preliminary study:

A preliminary stuy was carried out by doing two male and two female rats at 800mg/kg bodyweight.
The results of preliminary study indicated that the acute lethal oral dose to male and female rats on test item was in the region of 800 mg/kg bodyweight.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

739 mg/kg bw

Based on:

test mat.

95% CL:

> 619 - < 1 600

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

716 mg/kg bw

Based on:

test mat.

95% CL:

> 528 - < 1 512

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

762 mg/kg bw

Based on:

test mat.

95% CL:

> 500 - < 2 095

Mortality:

There were deaths among male and female rats at 500 mg/kg bodyweight and above. Deaths occured from Day 3 until Day 5. Among the decedents one female dosed at 800 mg/kg was sacrificed (Day 3 on humane grounds.

Slight bodyweight loss was record for all rats that died.

Macroscopic exmination of these animals revealed congestion of blood vessels and a free red substance in the cranial cavity in one male and female dosed at 800 mg/kg.

Clinical signs:

other: Pilo-erection was observed in all rats within four minutes of dosing and throughout the remainder if Day 1. This sign persisted and was accompanied on Day 1 and/or later intervals by: abnormal body carriage (hunched posture), abnormal gait (waddling), le

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of test item was estimated to be: Males and females combined 739 mg/kg bodyweight, 619 to 1600 mg/kg bodyweight.

Executive summary:

The study was carried out in compliance with the guidelines OECD No.401 "Acute Oral Toxicity" . Adopted: 24 February 1987.

Group of ten fasted rats (five males and five females) were given in a single dose by gaveage of the test substance, as supplied, at dose level of 500, 640 and 800 mg/kg bodyweight. All animals surviving treatment were killed and examined macroscopically on Day 15, the end of observation period.

 

There were deaths among male and female rats at 500 mg/kg bodyweight and above. Deaths occurred from Day 3 until Day 5. Among the decedents one female dosed at 800 mg/kg was sacrificed (Day 3 on humane grounds. Slightly bodyweight loss were recorded for all decedents. Macroscopic examination of these animals revealed congestion of blood vessels and free red substance in the cranial cavity in one male and one female dosed at 800 mg/kg.

 

 

Principal clinical signs of reaction to treatment were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decrease respiration rate, partially clised eyes, pallor of extremities, increased salivation, body tremors and cold body surface. Less commonly observed were clonic convulsions (characterized by repetitive symmetrical jerks or twitching of limbs), increased lacrimation, increase locomotor activity (when disturbed), hypersensitivity, arching of back, followed by falling over and pink extremities. Recovery of surviving rats, as judged by external appearance and behavior, was completed by either Day 6 0r 7 for rats at 500 mg/kg, Day 5 or 9 for rats at 640 mg/kg, or rats at 800 mg/kg, by Day 5 or 7.

 

Among surviving rats, slightly low bodyweight gains were recorded on Day 8 for two males and two females treated at 500 mg/kg, four female dosed at 640 mg/kg and one male and two females treated at 800 mg/kg; with the exception of one male treated at 800 mg/kg (which also showed a slightly low bodyweight gain on Day 15), these rats achieved anticipated gains on Day 15. All other rats achieved anticipated bodyweight gains throughout the study.

 

No macroscopic abnormalities were observed for animals killed on Day 15.

 

The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of test item was estimated to be:

 

Males and females combined: LD50: 739 mg/kg bodyweight, 95% confidence limits: 619 to 1600 mg/kg bodyweight

Male only: LD50: 716 mg/kg bodyweight, 95% confidence limits: 528 to 1512 mg/kg bodyweight

Female only: LD50: 762 mg/kg bodyweight, 95% confidence limits: 500 to 2095 mg/kg bodyweight

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

739 mg/kg bw

Quality of whole database:

1 (reliable without restriction)

Justification for classification or non-classification

Acute oral LD50: 300 -2000 mg/kg bw (actual value 739 mg/kg bw).

Therefore, according to Regulation (EC) 1272/2008 (amendment 286/2011), table 3.1.1, this substance should be classified as Acute toxicity category 4.