2-hydroxy-3-phenoxypropyl methacrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March - May 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

October 2008

Deviations:

yes

Remarks:

Due to technical reason, relative humidity values (maximum of 79 %) outside the expected range of 30-70 % were recorded during observation period. This deviation has no presumed impact on the outcome or integrity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-3-phenoxypropyl methacrylate

EC Number:

240-994-5

EC Name:

2-hydroxy-3-phenoxypropyl methacrylate

Cas Number:

16926-87-7

Molecular formula:

C13H16O4

IUPAC Name:

2-hydroxy-3-phenoxypropyl 2-methylprop-2-enoate

impurity 1

Reference substance name:

1-chloro-3-phenoxypropan-2-ol

EC Number:

225-310-5

EC Name:

1-chloro-3-phenoxypropan-2-ol

Cas Number:

4769-73-7

Molecular formula:

C9H11ClO2

IUPAC Name:

1-Chloro-3-phenoxy-2-propanol

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
171512
- Expiration date of the lot/batch:
23 December 2019

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Room temperature (15-25ºC, ≤ 70 RH%), protected from humidity (tigh closed container)

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Final dilution of a dissolved solid, stock liquid or gel:
200 mg/mL in the vehicle

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
Charles River Laboratories, Research Model and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation:
9-12 weeks old
- Weight at study initiation:
205-260 g
- Fasting period before study:
- Housing:
Individual caging (1 animal/cage)
- Diet: ssnif SM R/M "Autoclavable complete diet for rats and mice - breeding and maintenance" Batch number 382 24962, expiry date 30 April 2018 and Batch umber 883 29966, expiry date 31 October 2018. Fed ad libitum
- Water (e.g. ad libitum):
tap water from the municipal supply as for human consumption from 500 ml bottles, ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 25.0 ºC
- Humidity (%): 37-79 %
- Air changes (per hr): 15-20 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 22 March 2018 To: 08 May 2018

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): BCBS1795V
- Expiry date: 31 May 2018

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology,

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

PHPM did not cause any mortality at a dose level of 2000 mg/kg bw.

Clinical signs:

other: At the dose level of 2000 mg/kg bw, the following test item related symptoms were observed on Day 0: slightly decreased activity (2 out of 5 animals), piloerection (4 out of 5 animals), hunched back (4 out of 5 animals) and slight incoordination (5 out of

Gross pathology:

There was no evidence of treatment-related macroscopic changes at a dose level of 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item PHPM was found to be above 2000 mg/kg bw in female Crl:WI rats.

Executive summary:

 SUMMARY

 

An acute oral toxicity (up and down procedure) study was conducted with 5 female Crl:WI rats. Animals were treated with a single oral (gavage) dose of PHPM, at a dose level of 2000 mg/kg body weight (bw) followed by a 14-day observation period. The animals were fasted overnight prior to treatment and food was returned 3 hours after dosing.

 

Individual animals were dosed sequentially at no less than 48 hour intervals. The time intervals between doses were determined by the onset, duration and severity of clinical signs.

 

Animals were observed individually after dosing at 30 minutes, then 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter. Body weight was measured on Day -1, just before dosing and weekly thereafter. All animals were examined macroscopically at the end of the observation period.

 

Results

 

Mortality

The treatment with PHPM did not cause any mortality at a dose level of 2000 mg/kg bw.

 

Clinical Observations

At the dose level of 2000 mg/kg bw, the following test item related symptoms were observed on Day 0: slightly decreased activity (2 out of 5 animals), piloerection (4 out of 5 animals), hunched back (4 out of 5 animals) and slight incoordination (5 out of 5 animals). From Day 1 all the animals were symptom-free.

 

Body Weight and Body Weight Gain

One female animal showed slight body weight loss during the second week of the observation period. This change was considered incidental and minimal and not ascribed to treatment. There was no other treatment related effects on body weight or body weight gain during the observation period.

 

Macroscopic Findings

There was no evidence of treatment-related macroscopic changes at a dose level of 2000 mg/kg bw.

 

 

Conclusion:

Under the conditions of this study, the acute oral LD50 value of the test item PHPM was found to be above 2000 mg/kg bw in female CRL:WI rats.