Phenyl methacrylate

Endpoint summary

Description of key information

Oral LD50 (rate, female) = 500 mg/kg bw; OECD guideline 423; GLP

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:

2012-03-20 to 2012-04-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study. GLP.

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Wistar (RccHan™:WIST)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 151-164 g
- Fasting period before study: yes, overnight + 3-4 h after dosing
- Housing: in groups of 3, in suspended solid-floor polypropylene cages furnished with with woodflakes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: min. 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): min. 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 2000 mg/kg bw: unchanged; 300 mg/kg bw: arachis oil BP

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 mg/kg bw dose group: 30 mg/mL
- Amount of vehicle (if gavage): 300 mg/kg bw dose group: 10 mL/kg bw, 2000 mg/kg bw dose group: dosed unchanged, dose volume 1.19 mL/kg bw;
- Justification for choice of vehicle: the test item did not dissolve/suspend in distilled water

CLASS METHOD
- Rationale for the selection of the starting dose: In absence of data regarding the toxicity of the test item, 300 mg/kg bw was chosen as starting dose.

Doses:

300, 2000 mg/kg bw

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

A group of three fasted females was treated with the test item at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at dose levels of 300 and 2000 mg/kg bodyweight. Dosing was performed sequentially.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: bodyweights were recorded on days 0, 7, 14, or at death; clinical signs: 1/2, 1, 2, 4 h after dosing, once daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: necropsy of dead animals

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

act. ingr.

Mortality:

All animals of the 2000 mg/kg bw dose group were killed for humane reasons 1 h after dosing, due to occurrence of severe clinical signs of toxicity.
There were no deaths at a dose level of 300 mg/kg bw.

Clinical signs:

other: 2000 mg/kg bw: body tremors, prostration, ptosis, loss of righting reflex, laboured/noisy respiration 300 mg/kg bw: 2/6 animals: no signs of systemic toxicity 4/6 animals: ataxia, lethargy and/or hunched posture

Gross pathology:

No abnormalities were observed in animals treated with 300 mg/kg bw .
Clear liquid present in the stomach and epithelial sloughing of the gastric mucosa were noted at necropsy of animals treated with 2000 mg/kg bw.

According to Annex 2c of OECD Guideline 423, LD50 value of 500 mg/kg bw was estimated.

Interpretation of results:

other: Category 4

Remarks:

Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

The acute oral LD50 of PHMA in female rats is ca. 500 mg/kg bw.

Executive summary:

In an acute oral toxicity study according to OECD guideline 423 (adopted 17 December 2001), groups of fasted, 8-12 weeks old, Wistar strain rats (3 females) were given a single oral dose of PHMA at doses of 300 and 2000 mg/kg bw and observed for 14 days. A group of three fasted females was treated with the test item at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at dose levels of 300 and 2000 mg/kg bodyweight. Dosing was performed sequentially.

There were no deaths at a dose level of 300 mg/kg bw. All animals of the 2000 mg/kg bw dose group were killed for humane reasons 1 h after dosing, due to occurrence of severe clinical signs of toxicity (body tremors, prostration, ptosis, loss of righting reflex, laboured/noisy respiration). In the 300 mg/kg bw dose groups 2/6 animals showed no signs of systemic toxicity; in 4/6 animals ataxia,lethargy and/or hunched posture was observed.

The surviving animals showed the expected body weight gains.

No abnormalities were observed at necropsy in animals of the 300 mg/kg bw dose group. Clear liquid present in the stomach and epithelial sloughing of the gastric mucosa were noted at necropsy of animals treated with 2000 mg/kg bw.

Oral LD50 Female rats: according to Annex 2c of OECD Guideline 423, LD50 value of 500 mg/kg bw was estimated

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

500 mg/kg bw

Quality of whole database:

One relevant, reliable (Klimisch score = 1) and adequate study is available.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

One reliable (RL=1), relevant and adequate study is available to assess the acute oral toxicity of PHMA:

 

In an acute oral toxicity study according to OECD guideline 423 (adopted 17 December 2001), groups of fasted, 8-12 weeks old, Wistar strain rats (3 females) were given a single oral dose of PHMA at doses of 300 and 2000 mg/kg bw and observed for 14 days.A group of three fasted females was treated with the test item at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at dose levels of 300 and 2000 mg/kg bw. Dosing was performed sequentially.

There were no deaths at a dose level of 300 mg/kg bw. All animals of the 2000 mg/kg bw dose group were killed for humane reasons 1 h after dosing, due to occurrence of severe clinical signs of toxicity (body tremors, prostration, ptosis, loss of righting reflex, laboured/noisy respiration). In the 300 mg/kg bw dose groups 2/6 animals showed no signs of systemic toxicity; in 4/6 animals ataxia,lethargy and/or hunched posture was observed.

The surviving animals showed the expected body weight gains. No abnormalities were observed at necropsy in animals of the 300 mg/kg bw dose group. Clear liquid present in the stomach and epithelial sloughing of the gastric mucosa were noted at necropsy of animals treated with 2000 mg/kg bw.

Oral LD50 (rat, female): according to Annex 2c of OECD Guideline 423 an LD50 of 500 mg/kg bw was estimated

Justification for selection of acute toxicity – oral endpoint
OECD guideline study; GLP

Justification for classification or non-classification

Based on the available data, PHMA is classified as Hazard Category 4 for acute oral toxicity according to CLP, EU GHS (Regulation (EC) No 1272/2008) and labelled with H302 (harmful if swallowed) since the oral LD50 in rats is ca. 500 mg/kg bw (category definition: 300 mg/kg bw < ATE </= 2000 mg/kg bw).

According to Directive 67/548 EEC, PHMA is classified as Xn, Harmful, R22 (harmful if swallowed).