Acrylamide

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:

other: Well documented, guideline study conducted to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Acrylamide

EC Number:

201-173-7

EC Name:

Acrylamide

Cas Number:

79-06-1

Molecular formula:

C3H5NO

IUPAC Name:

prop-2-enamide

Details on test material:

- Name of test material (as cited in study report): Acrylamide in aqueous solution at 50%
- Substance type: organic
- Physical state: liquid
- Analytical purity: >99%
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: 50% in water
- Purity test date: no data
- Lot/batch No.: 616-003-00-0
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Credo, 69210 L' Arbresle, France
- Age at study initiation: approx. 6 weeks old
- Weight at study initiation: 197±7 g for the males, 152±6 g for the females
- Fasting period before study: 18 hours
- Housing: polycarbonate cages (48 cm x 27 cm x 20 cm)
- Diet: AO4 C pelleted diet (ad libitum)
- Water: ad libitum):
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h:12 h
IN-LIFE DATES: From: 01/10/1996 To:17/10/1996

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Dose Volume
(mg/kg) (ml/kg)
200 10
280 10
400 10

The administration was performed in a single dose by oral route using a stainless steel roundtipped probe fitted to a 2 or 5 ml glass syringe. The volume administered to each animal was adjusted according to body weight determined on the day of treatment.

Doses:

200, 280 and 400 mg/kg body weight

No. of animals per sex per dose:

5 females at 200 mg/kg, 5 females and 5 males at 280 mg/kg and 5 females at 400 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day.
- Frequency of weighing: prior to administration, then on days 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities

Statistics:

The LD50 value, expressed in milligrams of test substance per kilogram of animal (mg/kg), was calculated according to Probit-Analysis (Weber (1972)and Bliss (1938).The 70 to 95% confidence interval limits were calculated statistically according to Fieller's method (1944). Evaluation of the toxicity of the test substance following a single oral administration in rats should include the relationship, if any, between the animals' exposure to the test substance and the incidence and severity of all abnormalities including behavioural and clinical abnormalities, macroscopic lesions, body-weight changes, mortality and any other toxic effects.

Results and discussion

Preliminary study:

No applicable

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD0

Effect level:

200 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

354 mg/kg bw

Based on:

test mat.

95% CL:

305 - 458

Remarks on result:

other: 50% solution

Mortality:

Dose Male mortality Female mortality
200 mg/kg 0/5
280 mg/kg 1/5 0/5
400 mg/kg 4/5

Clinical signs:

other: At the 200 mg/kg dose-level, no clinical signs were observed. At the 280 mg/kg dose-level, no clinical signs were observed on day 1. One animal was found dead on day 2, and the other animals showed sedation or hypoactivity, piloerection, dyspnoea and trem

Gross pathology:

No apparent abnormalities were observed at necropsy in the animals which died during the study or those killed at the end of the observation period.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions, the oral LD50 in rats of acrylamide in aqueous solution at 50% was 354 mg/kg in female rats with 95% confidence interval limits of 305-458 mg/kg. Toxicity was comparable in males. In accordance with the ethic and scientific recommendations concerning the LD50 a more precise determination was not conducted. Based on the results of this study, it can be concluded that the acute oral LD50 of acrylamide in rats is 177 mg/kg. There were no mortalities (LD0) at the 200 mg/kg bw dose.