2-Hydroxyethylmethacrylate, reaction products with proyleneoxide and Phthalic anhydride

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Details on test material:

- Purity: 100%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adult (10 weeks)
- Weight at study initiation: 161-183 grams
- Fasting period before study: fasted overnight
- Housing: animals were individually housed in plastic solid bottom polycarbonate cage
- Diet: Harlan Teklad Global 16% Protein Rodent Diet® #2016. The diet was available ad libitum, except during fasting.
- Water: Filtered tap water was supplied ad libitum.
- Acclimation period: 14-17 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23ºC
- Humidity (%): 32-70%,
- Air changes (per hr): 13
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

2 groups of 3 for each dose level (12 dosed animals total)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were observed for mortality, signs of gross toxicity, and behavioural changes within 30 minutes post-dosing, during the first several hours after administration and at least once daily thereafter for 14 days after dosing.
-Frequency of weighing: Individual body weights of the animals were recorded shortly before the test substance was administered (initial) and again on Day 14 (termination) following dosing.
- Necropsy of survivors performed: All rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all euthanized animals.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: all animals survived

Mortality:

All animals survived

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

No gross abnormalities were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 >2000 mg/kg

Executive summary:

An acute oral toxicity test (acute toxic class method) was conducted with rats to determine the potential for the test substance to produce toxicity from a single dose via the oral route. At the request of the Sponsor, a full test was conducted using a default starting dose level of 300 mg/kg administered to three healthy female rats by oral gavage. Due to the absence of mortality in these animals, three additional females received the same dose level, simultaneously. Since these animals survived, six additional animals in two consecutive groups of three rats each were dosed at the next highest dose level of 2000 mg/kg. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Day 14 (termination) following dosing. Necropsies were performed on all animals at terminal sacrifice.

All animals dosed at 300 and 2000 mg/kg survived and exhibited no clinical signs or body weight loss during the study. No gross abnormalities were noted for these animals when necropsied at the conclusion of the 14-day study. Under the conditions of this study, the acute oral LD₅₀ of the test substance is greater than 2000 mg/kg of body weight in female rats.