2-hydroxyethyl methacrylate

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 5000 mg/kg
Acute dermal toxicity: LD50 > 5000 mg/kg
Acute inhalation toxicity: no data available, no toxicity is expected

2-Hydroxyethyl methacrylate is of low acute oral toxicity (LD50 > 5000 mg/kg) (Sterner, Stiglic 1977).
A study on dermal toxicity of HEMA is not available. The structurally very similar substance Hydroxypropyl methacrylate (CAS 27813-02-1) is of low dermal toxicity (LD50: > 5000 mg/kg) (Rohm & Haas, 1982).

Due to the low vapour pressure of HEMA, inhalation is not an expected route of exposure.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail.

Qualifier:

according to guideline

Guideline:

other: Appraisal of the safety of chem by the Staff of the Division of Pharmacology, FDA, 1959 in food, drugs and cosmetics

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

Test substance: as prescribed by 1.1 - 1.4
pH: 6.0

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Zucht Winkelmann, Paderborn, Germany
- Age at study initiation:
- Weight at study initiation: 150 - 200 g
- Fasting period before study: 16 hrs prior to test start
- Diet (e.g. ad libitum): Laborytory standad diet: Saniff/Intermas
- Water, ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 45-55
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 6.30 ml/kg
Rationale for the selection of the starting dose: range finding test

Doses:

3.18 ml/kg = 3.40 g/kg
3.98 ml/kg = 4.26 g/kg
5.00 ml/kg = 5.35 g/kg
6.30 ml/kg = 6.74 g/kg

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: ca. 10 minutes, 1 h, 3 h, 24 h, 4 days, 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, reactions, emotions, nerval syptoms (i.e. tremor, ataxie, body tonus, reflexes, piloerection; body temperature

Statistics:

Litchfield & Wilcoxon, in combination with Gauß integral

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 564 mg/kg bw

Based on:

test mat.

Mortality:

Mortalities occured within 24 h

Group Dose 24 h 14 days
I 3.40 g/kg 1/10 1/10
II 4.26 g/kg 1/10 1/10
III 5.35 g/kg 4/10 4/10
IV 6.74 g/kg 8/10 8/10

Clinical signs:

other: After autopsy of the acute mortalities hemorraghes of the stomach- and colon mucosa where found. At test end no pathological- or anatomical changes where found in the cranium-, chest- and abdominal cavity were found.

Gross pathology:

The test substance elicted in increasing extend reduced activity, tremor , convulsion, ataxia, postural anomalies, reduced grip- and limb tonus, increased body temperature and pilo ecerection. These symptomes appeared ca. 10 minutes after application and remained partly 24 hrs. After this all survived animals showed again normal habitus during the whole observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, 2-hydroxyethyl methacrylate is not required to be classified for its acute toxicity potential according to EU Regulation No 1272/2008 and UN-GHS requirements, respectively.

Executive summary:

2 -Hydroxyethyl methacrylate was tested in a acute oral toxicity test in rats at concentrations up to 6740 mg/kg according to "Appraisal of the safety of chem by the Staff of the Division of Parmacology, FDA, 1959 in food, drugs and cosmetics". LD50 for acute oral toxicity was determined to be >5000 mg/kg. Therefore the substance is not classified according to EU Regulation No 1272/2008 and UN-GHS requirements, respectively.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

1.HYPOTHESIS FOR THE ANALOGUE APPROACH
2-Hydroxyethyl methacrylate is of low acute oral toxicity (LD50 > 5000 mg/kg) (Sterner, Stiglic 1977).
Due to the low vapor pressure of HEMA inhalation is not an expected route of exposure. A study on dermal toxicity with HEMA is not available. The structurally very similar substance Hydroxypropyl methacrylate (CAS 27813-02-1) is of low dermal toxicity (LD50: > 5000 mg/kg) (Rohm & Haas, 1982). It can be expected that 2-Hydroxyethyl methacrylate is of the same low acute dermal toxicity like Hydroxypropyl methacrylate
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Read across to cover endpoint requirements is performed only from studies with pure substance. The purity of the source substance Hydroxypropyl methacrylate (CAS 27813-02-1) in the study was reported to be 99.2 %, the purity of the target substance 2-Hydroxyethyl methacrylate (868-77-9) is ca. 98 %. Typical impurity of both substances is methacrylic acid (CAS 79-41-4) in the range of 0.1 to 1 %, typically 0.1 %
ANALOGUE APPROACH JUSTIFICATION
Data from Hydroxypropyl methacrylate can be read across because the source substance is structurally very similar to 2-Hydroxyethyl methacrylate.
2-Hydroxyethyl methacrylate and Hydroxypropyl methacrylate have common functional groups as they are both esters of methacrylic acid and additionally they have hydroxyalkyl groups which are only slightly different in the length of the alkyl group and the position of the hydroxy group. Physico chemical properties, particularly log Pow, are in the same range. Both substances are predicted to be rapidly absorbed to skin (Heylings, 2013) and are both skin sensitizers. All these similarities together with the fact that both substances are of low acute oral toxicity (LD50 > 5000 mg/kg) as well as in the acute dermal toxicity study of HPMA at a concentration > 5000 mg/kg should allow to estimate acute dermal toxicity of HEMA by read across on experimental data of the acute dermal toxicity of HPMA.
Consequently the acute dermal toxicity of HEMA is determined to be > 5000 mg/kg by read acoss with HPMA

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on read aross with the structurally similar substance hydoxypropyl methacrylate the acute dermal LD50 was determined to be >5000 mg/kg.

Executive summary:

No acute dermal toxicity study with 2-hydroxyethyl methacrylate is available. The acute dermal toxicity was determined by read across with hydroxypropyl methacrylate. No mortality occured in a limit test with 6 rabbits at test a concentration of 5000 mg/kg. Therefore LD50 of 2-hydroxypropyl methacrylate is determined to be > 5000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

>= 5 000 mg/kg bw

Additional information

The oral LD₅₀of HEMA in rats was determined to be 5564 mg/kg. This study (Sterner, 1982) was assigned a Klimisch rating of 2, reliable with restriction. Dose-related symptoms included reduction in activity, tremor, disturbance of coordination or gait, reduced muscle tonus in limbs, elevated temperature and piloerection. Other available studies were reviewed and judged to be not reliable or not assignable.

No acute dermal toxicity with HEMA itself is available. Dermal toxicity was assessed by read across with Hydropxypropyl methacrylate (HPMA, CAS 27813-02-1). The dermal LD₅₀ of HPMA in rabbits was determined to be > 5000 mg/kg. This study (Rohm and Haas 1982) was assigned a Klimisch rating of 2, reliable with restriction. No clinical symptoms of intoxication were noted. Animals’ skin presented with erythema but no edema. Due to the structural analogy, the anticipated comparable dermal absorption (Heylings 2013) and the low observed acute toxicity after oral administration of HEMA and HPMA, this study with HPMA is used as read across for HEMA.

 

No acute inhalation toxicity test data are available for HEMA. Taking into account the low vapour pressure and saturated vapour concentration, inhalation is not a relevant route of exposure as confirmed by actual workplace concentrations (see attachment in IUCLID dataset chapter 13 Assessment reports). Potentially toxic concentrations cannot be reached due to the low vapour pressure.

Justification for classification or non-classification

The oral LD50 of HEMA in rats was determined to be >= 5000 mg/kg. By read-across to HPMA, the dermal LD50 in rabbits was determined to be > 5000 mg/kg. Data on acute inhalation toxicity are not available but no acute toxicity by inhalation is expected due to the low vapor pressure.

Therefore the substance is not classified according to EU Regulation No 1272/2008 and UN-GHS requirements, respectively.