2,3-epoxypropyltrimethylammonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

other: EU Risk Assessment report

Adequacy of study:

other information

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Although the EU risk assessment report is secondary literature, all data and risk assessment for the human, health and the environment have been evaluated and reviewed by Finland prior to publication. The risk assessment report has been submitted to final approval and published in the Official Journal of the European Union C157/10 dated on 21.06.2008. Thus, it is considered the information reported are reliable with the restrictions that reliability of the data presented has not been assessed again.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

European Union Risk Assessment 2,3-epoxypropyltrimethylammonium chloride CAS RN 3033-77-0 Einecs No: 221-221-0

Author:

EC

Year:

2008

Bibliographic source:

Risk Assessment. Final approved version. Rapporteur: Finland (FIN). European communities. Printed in Italy. 147pp

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Remarks:

Study performed before GLP establishment

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,3-epoxypropyltrimethylammonium chloride

EC Number:

221-221-0

EC Name:

2,3-epoxypropyltrimethylammonium chloride

Cas Number:

3033-77-0

Molecular formula:

C6H14NO.Cl

IUPAC Name:

N,N,N-trimethyl(oxiran-2-yl)methanaminium chloride

Details on test material:

- Name of test material (as cited in study report): EPTAC
- Physical state: aqueous solution
- Analytical purity: 71.9 % test substance in aqueous solution
- Impurities (identity and concentrations): The original solution had about 10% impurities

Test animals

Species:

rat

Strain:

other: SPF Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

no details

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: the 71.9% test substance in aqueous solution was diluted with water to 20% EPTAC
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 8.5 mL/ kg

Doses:

4.0; 4.8; 5.8; 6.9 and 8.5 mL/kg

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, macroscopic observations

Statistics:

The LD50 value was determined according to the method of Weil

Results and discussion

Preliminary study:

No data

Effect levels

Effect levels 1

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 1.39 mL/kg bw

Based on:

test mat.

95% CL:

>= 1.18 - <= 1.52

Effect levels 2

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 1 513 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Assuming a density of 1129 mg/cm3

Effect levels 3

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 1 088 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Assuming a density of 1129 mg/cm3 and the pure substance (100%)

Mortality:

See details in table 7.2.1/1. The animals died between 1 and 48 hours.

Clinical signs:

other: Within few hours of dosing, the rats showed sedation, dark-coloured eyes, tremors and conculsions. Later, Diarrhoea and loss of conscioussness were observed. The surviving animals appeared to have recovered at the end of the observation period.

Gross pathology:

No treatment-related alterations

Other findings:

No other findings related

Any other information on results incl. tables

Table 7.2.1/1: Mortality after an acute oral exposure to EPTAC

Dose (mL 20% EPTAC/kg)	Males	Females
4.0	0/5	1/5
4.8	1/5	1/5
5.8	1/5	2/5
6.9	0/5	4/5
8.5	4/5	4/5

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, EPTAC is classified as Acute tox. 4 (H302, harmful if swallowed) according to the CLP regulation (No. 1272/2008 EC) and as harmful if swallowed (Xn, R22) according to the Directive 67/548/EEC.

Executive summary:

In an acute oral study (Degussa, 1981a), considered as the Key study, five male and five female young adult, SPF-albino rats per dose and per sex were administered a single oral dose of 2,3-Epoxypropyltrimetylammonium Chloride (EPTAC) at volumes ranging from 4.0, 4.8, 5.8, 6.9 and 8.5 ml/kg in aqueous solution. The 71.9% test substance in aqueous solution was diluted with water to 20% EPTAC (v/v). The original solution had about 10% impurities, apparently resulting from the synthesis. According to the information available, it can be considered that the study was performed similarly to the Guideline OECD No. 401.

 

The rats were observed for signs of toxicity for 14 days after which an autopsy was conducted on the survived animals. Within few hours of dosing, the rats showed sedation, dark-coloured eyes, tremors and convulsions. Later, diarrhoea and loss of consciousness was observed. No details were given about the doses at which the non-lethal effects occurred. The surviving animals appeared to have recovered at the end of the observation period. When observed macroscopically, animals had no treatment-related alterations. Mortality was observed at all tested doses. The animals died between 1 and 48 hours. An LD₅₀value of 1.34 ml/kg (CI95 1.18 and 1.52) for the 71.9% test substance was calculated according to the method of Weil. This can be converted to approximate milligrams using the density value of 1129 mg/cm³available for 70% EPTAC. The resulting LD₅₀is 1513 mg/kg of the 71.9% test substance or 1088 mg/kg pure EPTAC.

 

In another study(Shellengberger, 1962), considered as a supporting study, an LD₅₀value of 1720 mg/kg obtained from an experiment where ten rats per dose group were administered orally 1250, 1575, 1988, 2500 mg/kg of EPTAC. In the highest dose group, all animals died within 15 hours, in the 1988 mg/kg dose group, 7/10 animals died, all within 1 day, at 1575 mg/kg dose group 3/10 rats died within 2 days and in the lowest dose group 2/10 died within 3 days. Transient depression at lower doses, dyspnea, salivation sanguineous ocular discharge and clonic convulsions at higher doses were recorded as clinical signs. The reporting of study details was limited.

 

Considering the LD₅₀of 1088 mg/kg bw obtained for the pure substance, EPTAC is classified as Acute tox. 4 (H302, harmful if swallowed) according to the CLP regulation (No. 1272/2008 EC) and as harmful if swallowed (Xn, R22) according to the Directive 67/548/EEC.