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Description of key information

Acute oral toxicity rat: LD50: 1815 mg/kg; signs of neurotoxicity at the lowest tested doses in the key and supportive study

Acute dermal toxicity rat: LD0: > 1600 mg/kg

Short-term repeated dose toxicity rat: microscopic signs of respiratory irritation.

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:
06-03-1986 - 26-03-1986
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:
adopted 12-May-1981
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Supplier: Evonik Röhm GmbH, Darmstadt, Germany
- Purity: > 90%
- Lot/batch No.: 86013
- Expiration date of the lot/batch: 30 April 1986
- Stability of test article dilution: stable for at least 2 hr
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
mTEST ANIMALS
- Source: outbred, SPF Wistar rats, Kleintierfarm Madoerin AG, Fuellingsdorf, Switzerland
- Age at study initiation: 10 to 12 weeks
- Weight at study initiation: Males: 187 - 259 g; Females: 168 - 197 g
- Fasting period before study: 12 - 18 hr
- Housing: Groups of 5 in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, Muttenz, Switzerland). Cages were cleaned
twice weekly during the test period.
- Diet: ad libitum, pelleted standard Kliba 343, Batch 36/85
- Water: ad libitum tap water from Itingen, Switzerland
- Acclimation period: One week under laboratory conditions, after veterinary examination.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 40 - 70 %
- Air changes (per hr): 10 - 15 air changes per hr
- Photoperiod (hrs dark / hrs light): 12 hr artificial flourescent light/ 12 hr dark, music/light period.
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Carboxymethylcellulose-Na-solution (suspension: 4 %)
- Justification for choice of vehicle: no data
- Supplier: Fluka AG, Switzerland
- Lot/batch no. (if required): no data
- Purity: no data, but commerial available substance

MAXIMUM DOSE VOLUME APPLIED: 20 mL

Doses:
1000, 2000 and 3000 mg/kg
No. of animals per sex per dose:
5 males, 5 females per dose group
Total number of animals: 15 males, 15 females
Control animals:
no
Details on study design:
- Test article preparation: immediately prior to dosing
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Mortality/Viability: four times during test day 1, and daily during days 2 - 15
Body weights: Test day 1 (pre-administration, 8 and 15
Symptoms: Each animal was examined for changes in appearance and behavior four times during day 1
and daily during days 2 - 15. All abnormalities were recorded.
- Necropsy of survivors performed: all animals were necropsied.
- Other examinations performed: clinical signs and symptoms, body weight, mortality, macroscopic findings
Statistics:
The LOGIT-model (COX, Analysis of binary data, London 1977) was applied to estimate the toxicity value. Additionally, the 90, 95 and 99% confidence intervals for the toxicity for each sex slope of the dose response line were estimated.
Preliminary study:
No further information mentioned in the study report.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 815 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 461 - <= 2 192
Remarks on result:
other: LOGIT-estimation
Sex:
male
Dose descriptor:
LD50
Effect level:
1 938 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 353 - <= 3 015
Remarks on result:
other: LOGIT-estimation
Sex:
female
Dose descriptor:
LD50
Effect level:
1 653 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 035 - <= 2 226
Remarks on result:
other: LOGIT-estimation
Key result
Sex:
male/female
Dose descriptor:
other: LOAEL
Remarks:
acute neurotoxicity
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: sedatation as sign for neurotoxicity was observed at 1000 mg/kg, the lowest dose was observed
Mortality:
sse table 1
Clinical signs:
The following symptoms were observed:
1000 mg/kg: sedation, ruffed fur (females)
2000 mg/kg: sedation, ataxia, ventral body position, curved body position, emaciation (females),
ruffed fur
3000 mg/kg: sedation, ataxia, ventral body position, latera-abdominal position,curved body position,
ruffed fur (females), lacrimation (females)
.The surviving rat had recovered within 2 to 14 days.

2000 mg/kg:
dead - lung: dark-red mottled; dark-red discolored; reddish discolored
stomach: meteorism; enlarged small testines: meteorism; yellowish contents
stomach/intestines: meteorism, severe killed - no pathologic changes
3000 mg/kg:
dead - lung: dark-red discolored; dark-red to black discolored; dark-red, light mottled
liver: light mottled, ventral stomach: meteorism, severe; filled with test article, totally filled with test article; cloudy fluid
intestines: red to yellowish contents, yellowish, foamy mass; yellowish mass; yellowish fluid.
Body weight:
Male animals of the 1000 mg/kg and 2000 mg/kg dose group gained body weight, also female animals but lower in the 100 mg/kg dose group. Female animals in the 2000 mg/kg dose group did not gain body weight.
Gross pathology:
Pathology: No substance related gross pathological changes
The following macroscopic organ changes were observed:
1000 mg/kg: killed - lung: dark-red mottled; no pathologic changes.
2000 mg/kg: dead - lung: dark-red mottled; dark-red discolored; reddish discolored

Table 1: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

Dose
(mg/kg bw)

Mortality (dead/total 5)

Time range of deaths (hours)

Male

Female

Combined

Control

-

 -

 -

 -

1000

 0

 0

2000

 4

5 - 24 

3000

 5

1 - 5 

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
According to the test result: LD50(15days): 1815 mg/kg bw the test substance methacrylamide has to be classified as slightly toxic in respect of its acute oral toxicity.
Executive summary:

In an acute oral toxicity study according to OECD guidline 401 with GLP, groups of fasted male and female SPF Wistar rats were given a single oral dose of Methacrylamide commercial grade at doses of  1000, 2000 and 3000 mg/kg bw and observed for 15 days.

 

Oral LD50 Combined = 1815 mg/kg  bw (95% C.I. 1461 - 2192 mg/kg bw)

Methacrylamide is of slightly oral toxicity (GHS category 4) based on this LD50 test in males and females.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 815 mg/kg bw
Quality of whole database:
Key study acc. OECD guideline, with GLP. 3 dose groups were tested, 5 animals per dose group. The study result is supported by several studies with less quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
There is no study available acc. to OECD 403. In a 14 day range finding study in concentrations up to 0.286 mg/l no death occured.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: only short documentation
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: no data
GLP compliance:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Duration of exposure:
4 hrs
Doses:
20% or 10% solutions
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
In this study, 20% or 10% solution of methacrylamide was applied for 4 hours to abdominal skin.
Sex:
not specified
Dose descriptor:
LDLo
Remarks:
4 hours application
Effect level:
> 1 600 mg/kg bw
Based on:
test mat.
Executive summary:

In an acute dermal toxicity study 10 rats per dose group were dermally exposed to 20- and 10-% solutions of Methacrylamide in 60% ethanol, (96 %, denatured with 2 % Benzene) 20 % Propanol and 20 % water for 4 hours to 10 % of body surface area. No mortality occured. Only temporary apathie just like the control group with the vehicle was observed.

Dermal LD0 > 1600 mg/kg

Methacrylamide is of low toxicity

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
No full OECD 402 guideline study is available for methacrylamide. But available data of BASF study with short exposure (4 h) with an LDL > 1600 mg/kg.
Based on in silico prediction of dermal penetration of methacrylamide into the skin max. penetration of methacrylamide into rats was estimated to be 170.5 mg/kg bw. This concentration is ca. 10 % of the the acute LD50 in rats of 1815 mg/kg bw (Röhm, 1986) which supports the assumption that methacrylamide is of low toxicity. This assumption is also supported by the very short ducumented data of Porokhova (1980): LD 50 dermal in rats and mice: > 6000 mg/kg bw

Additional information

Justification for classification or non-classification

- Methacrylamide is acute toxic by oral exposure. LD50 rat oral (OECD 403) is 1815 mg/kg bw. According to CLP , methacrylamide is classified with Hazard category Acute 4, H302, Harmful if swallowed.

- Acute dermal toxicity is not predicted based on available data and in silico prediction of skin penetration.

- Acute toxicity by inhalation is not predicted due to low vapour pressure.

- Methacrylamide aerosols caused irritative effects in the respiratroy system of rats after short-term repeated dose exposure. Thus, methacrylamide is classified with STOT-SE category 3/ respiratory system, H335 according to CLP.

- Methacrylamide caused neurotoxic effects in rats after single exposure to < 2000 mg/kg bw. According to CLP, methacrylamide is classified with STOT-SE category 2, H302, for its neurotoxicological potential.