Methacrylamide

Endpoint summary

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:

other: 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-abdom

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	0	-
2000	2	4	3	5 - 24
3000	5	5	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:

LD0

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

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.