Registration Dossier

Diss Factsheets

Administrative data

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-Hydroxypropyl methacrylate is of low acute oral toxicity.  [MHLW, 1996: LD50 > 2000 mg/kg, Rohm & Haas, 1982: > 5000 mg/kg, Rohm & Haas, 1961: > 5000 mg/kg).
 Hydroxypropyl methacrylate is of low dermal toxicity (LD50: > 5000 mg/kg) (Rohm & Haas, 1982).


Due to the low vapour pressure of HPMA, 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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Supplier: Mitsubishi Rayon Co., LTD. (Tokyo, Japan),
Purity 98%
Lot No. 0348402.
Imputity: <=2 % of dipropylene glycol monomethacrylate
Storage conditions: in an airtight container with preventing light before use, storage at room temperature
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
Details on animals:
Four weeks old Sprague-Dawley (Crj:CD(SD), SPF) rats
bought from Charles River Japan, Inc. They were put in quarantine and
acclimation for 8 days before use.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 deg C
- Humidity (%): 40-70%
Route of administration:
oral: gavage
Vehicle:
other: Water for injection
Details on oral exposure:
24 hour exposure
Doses:
0 (vehicle), 500, 1000, 2000 mg/kg
No. of animals per sex per dose:
5males, 5 females
Control animals:
yes
Details on study design:
Observation period: 14 days
Statistics:
Statistics Analysis: Mean body weights and their standard deviations
were calculated for every group.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Mortality:
No mortality in any group
Clinical signs:
other:
Body weight:
other body weight observations
Remarks:
-Male and female The body weight gains of each group showed similar to that of control group during the test period.
Gross pathology:
-Male and female
--Survival animals (All animals)
No abnormalities were found in the surviving animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 was determined to be >2000 mg/kg for male and female rats.
Executive summary:

Hydroxypropyl methacrylate was tested in an acute oral toxicity test acc. OECD 401 in CD rats at concentrations of 0, 500, 1000 and 2000 mg/kg bw. 5animals per sex and dose group were tested. No mortality has been observed in any dose group. Therefore LD50 is considered to be > 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
One OECD 401 Guideline study is available which has been performend under GLP at concentrations up to 2000 mg/kg with original documentation in Japanese and an abstract in English (MHLW 1996). Supporting information is available with two non GLP studies at > 5000 mg/kg of Rohm & Haas and sufficient documentation. (Rohm & Haas 1982 and 1961, respectively).
Additional test data are available in rats and mice where animals.

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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance, as received, was held under an impervious cuff in continuous 24-hr contact with the closely clipped skin of New Zealand White rabbits.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Rocryl(TM) 410
- Purity: 99.2 %
Impurities: low boilers: 0.03 %
methacrylic acid: 0.2 %
high boilers: 99 %
propylene oxide: 5 ppm
propyleneglycol-
dimethacrylate : none detected
Inhibitor : hydroquinone monomethyl ether: 5 ppm
CB : 0.10 %
- Batch No.: JK-6673-2
Species:
rabbit
Sex:
male
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Application: 24 hours, after the exposure time cuffs were removed and the test substance was gently wiped from the application sites with paper towels.
Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
6 males
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
0/6 animals died
Clinical signs:
other: effects observed in 6/6 animals, not further specified
Gross pathology:
effects observed in 6/6 animals, not further specified
Other findings:
Skin irritation: well defined erythema, no edema. The skin irritation was recovered on day 5 after dosing.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 was determined to be >5000 mg/kg.
Executive summary:

The acute dermal toxicity of HPMA was tested in a limit test in a concentration of 5000 mg/kg in 6 New Zealand White rabbits. 0/6 animals died. LC50 dermal of HPMA is considered to be > 5000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
>= 5 000 mg/kg bw
Quality of whole database:
The key study is of limeted documentation. Additional handbook data support the key study.

Additional information

Rats given a single oral dose of HPMA of up to 2000 mg/kg survived exposure. The only clinical symptom of intoxication was salivation in a few animals administered the 2000 mg/kg dose. This study was compliant with OECD 401 and was assigned a Klimisch rating of 1, reliable without restriction. Supporting information is available with a non GLP limit test  in rats of Rohm & Haas (1982) at a test concentration of 5000 mg/kg, where no animals died and a test in rats with  6 test concentrations from 100 mg/kg bw up to 31,600 mg/kg bw (Rohm & Haas 1996) which confirms an LD50 oral > 5000 mg/kg.


The dermal LD50of 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. Additional less documents studies support the key studies.


 


No acute inhalation toxicity test data are available for HPMA. Taking into account the low vapour pressure and saturated vapour concentration of the two chemicals, inhalation is not a relevant route of exposure as confirmed by actual workplace concentrations. Potentially toxic concentrations cannot be reached due to the low vapour pressure (0.11 hPa @ 20°C).

Justification for classification or non-classification

The oral LD50 of HPMA in rats was determined to be >= 5000 mg/kg. 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.