2-(3-oxazolidinyl)ethyl methacrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9/19/2001-10/3/2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Japan 59 NohSan Notification No. 4200, Acute Oral Toxicity Study

Test guideline 4

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(3-oxazolidinyl)ethyl methacrylate

EC Number:

256-260-2

EC Name:

2-(3-oxazolidinyl)ethyl methacrylate

Cas Number:

46235-93-2

Molecular formula:

C9H15NO3

IUPAC Name:

2-(1,3-oxazolidin-3-yl)ethyl 2-methylprop-2-enoate

Test material form:

liquid

Remarks:

yellow

Test animals

Species:

rat

Strain:

other: Crl:CD BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

Adult male and female Crl:CDaBR rats were obtained from Charles River Laboratories, Raleigh, NC. Upon arrival, all animals were examined for physical abnormalities and quarantinedlacclimated for approximately one week. The animals were individually housed in suspended stainless steel cages (18x34x20cm) with wire mesh fronts and bottoms. Cages were suspended above absorbent-paper pan liners, which were changed 3 times a week. Throughout the test period, all rats had free access to water (via automatic watering) purified by reverse osmosis and PMI Certified Rodent Diet 5002(C) (Purina Mills Inc., Richmond, IN). The animal room was environmentally controlled with controls set to maintain a temperature of approximately 23°C and a relative humidity range of 30-70%. The temperature and relative humidity were monitored 24 hrs a day. During the study, the average daily temperature was approximately 22°C and the average daily relative humidity ranged from 44 to 54%. Any excursions beyond these ranges were minimal and did not affect the integrity of the study. Temperature and relative humidity remained in compliance with acceptable ranges defined in the "Guide for the Care and Use of Laboratory Animals" ISBN No. 0-309-05377-3, Revised 1996. The light cycle was automatically controlled, 12 hrs on and 12 hrs off.

Prior to treatment, rats were selected from a healthy stock population, assigned to the study group using a computer-generated sequence of random numbers, identified by uniquely numbered ear tags, and fasted overnight. At the time they were dosed, the males were approximately 8 weeks old and the females were approximately 9 weeks old. The fasted body weights ranged from 208 to 242 g for males and from 182 to 201 g for females.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The undiluted test substance was was administered to male and female rats at 250, 750 or 1250 mgkg body weight. Dose was calculated on an "as is" basis; no adjustment was made for percent active ingredient. No analytical verification of the dosing solution was performed since the test substance was administered undiluted.

Doses:

250, 750, and 1250 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

All animals were observed for signs of ill health, or reaction to treatment at approximately 1,2 and 4 hrs after dosing and once daily thereafter for 14 days. Body weights were recorded on day 0 (prior to dosing) and on days 7 and 14. Decedents were necropsied as they were found. Surviving rats were euthanized on day 14 and necropsied. Necropsy consisted of a gross examination of organs in situ.

Statistics:

The mortality incidences of males and females were compared across doses with a categorical data modeling procedure using SAS CATMOD (SAS Institute Inc. SAS User's Guide: Statistics, Version 6 Edition, p 405-517. Cary, NC: SAS Institute Inc., 1990). The criterion of statistical significance was 0.05. Since the results did not indicate a significant difference between the mortality responses across dose groups for males and females, the LD50 was calculated on the pooled (male and female combined data) mortality incidences at each dose.

The LD5o and slope were calculated from the logarithm of the doses and the incidences of mortality using a SAS PROBIT procedure (SAS Institute Inc. SAS User's Guide: Statistics, Version 6 Edition, p 1324-1350. Cary, NC: SAS Institute Inc., 1990) based on the method of D.J. Finney (Probit Analysis, Third Edition, London: Cambridge University Press, 1971). The procedure was unable to determine the 95% confidence limits.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

763 mg/kg bw

Based on:

test mat.

Mortality:

Two male and 2 female animals at 750 mg/kg died by day 3 and all rats at 1250 mg/kg died by day 1.

Clinical signs:

other: No clinical signs of toxicity were noted in males at 250 mglkg during the 14-day observation period. Scant feces was noted in females at 250 mglkg on day 1 only. Numerous clinical signs of toxicity were noted in males and/or females at 750 and/or 1250 mg/

Gross pathology:

Necropsy of the decedents in both sexes at 750 and 1250 mg/kg revealed numerous gastrointestinal changes. These included: stomach: distended, thickened, contains clear fluid, glandular portion reddened and/or sloughing, contains gelatinous material and intestine reddened. Carcass autolysis was also noted. Necropsy of the survivors at 250 mg/kg (both sexes) and 750 mg/kg (males) revealed no gross changes. One female survivor at 750 mg/kg was found with stomach wall thickened.

Other findings:

The acute oral LD50 in male and female rats was 763 mg/kg. The log probit slope of the dose-mortality data (probit incidence versus log dose) was 7.72 in this study.

Any other information on results incl. tables

Table 1. Mortality

Dose (mg/kg)	250	750	1250
Males	0/5	2/5	5/5
Females	0/5	2/5	5/5
Combined sexes	0/10	4/10	10/10

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 for OXEMA in male and female rats was 763 mg/kg bw.

Executive summary:

The acute oral toxicity of Monomer OXEMA was assessed in Crl: CD®BR rats. Three groups of five male and five female rats/groups were gavaged with the test substance, as received, at 250,750 or 1250 mg/kg body weight. Two male and 2 female animals at 750 mg/kg died by day 3 and all rats at 1250 mg/kg died by day 1. No clinical signs of toxicity were noted in males at 250 mg/kg during the 14-day observation period. Scant feces were noted in females at 250 mg/kg on day 1 only. Numerous clinical signs of toxicity were noted in males and/or females at

750 and/or 1250 mg/kg. These included: soft, scant/no feces, red or tan stained muzzle, passiveness, ataxia, yellow/brown stained anogenital area, and red-stained eyes. These clinical signs were evident beginning on day 0 and continued through day 5. Body weight gain among survivors in both sexes at 750 mg/kg was decreased (32-39%) when compared to historical control values. There was no treatment related effect on body weight gain among both sexes at 250 mg/kg. Necropsy of the decedents in both sexes at 750 and 1250 mg/kg revealed numerous gastrointestinal changes. Necropsy of the survivors at 250 mg/kg (both sexes) and 750 mg/kg (males) revealed no gross changes. One female survivor at 750 mg/kg was found with stomach wall thickened. The acute oral LD50 for OXEMA in male and female rats was 763 mg/kg.