Reaction products of tetraethylenepentamine and maleic anhydride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-04-23 to 2014-06-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented study performed according to OECD TG 420 and EC B.1.bis guideline, in compliance with GLP. No deviations were noted.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

liquid: viscous

Details on test material:

- Name of test material (as cited in study report): XTA 823- Substance type: yellow slightly viscous liquid- Physical state: liquid- Purity (solids content): 49.8%- Purity test date: no data- Lot/batch No.: BLW060113- Expiration date of the lot/batch: not supplied- Stability under test conditions: no data- Storage condition of test material: at room temperature in the dark-Other: - Production date: 2014-10-02

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: 6 female Wistar strain rats, RccHan (TM):WIST; supplied by Harlan Laboratories UK Ltd., Oxon, UK- Age at study initiation: 8-12 weeks (nulliparous and non-pregnant)- Weight at start of study: 166 - 180 grams - Fasting period before study: overnight immediately before dosing until approximately 3 to 4 hours after dosing- Housing: in groups of up to 4 in suspended solid-floor polypropylene cages furnished with woodflakes.- Diet (e.g. ad libitum): ad libitum, 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK- Water (e.g. ad libitum): ad libitum- The diet, drinking water and bedding were routinely analyzed and were considered no to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study. - Acclimation period: at least five daysENVIRONMENTAL CONDITIONS- Temperature (°C): 19 - 25 °C- Humidity (%): 30 - 70%- Air changes (per hr): at least 15 changes per hour- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

VEHICLE- Concentration in vehicle: 30 mg/ml- Amount of vehicle (if gavage): 10 ml/kg- Justification for choice of vehicle: no data- Lot/batch no. (if required): no data- Purity: no dataMAXIMUM DOSE VOLUME APPLIED: 10 ml/kg (dose of 300 mg/kg), 1.70 ml/kg (dose of 2000 mg/kg)DOSAGE PREPARATION (if unusual):- For the purpose of the 2000 mg/kg dose level the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. - For the purpose of the 300 mg/kg dose level the test item was freshly prepared, as required, as a solution in distilled water.- The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration. - No analysis was carried out to determine the homogeneity, concentration or stability of the test item formulation. This exception is considered not to affect the purpose or integrity of the study.

Doses:

300 - 2000 mg/kg (50% solution)

No. of animals per sex per dose:

1 animal at 300 mg/kg5 animals at 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days- Frequency of observations and weighing: clinical observations: 1/2, 1, 2 and 4 hours after dosing and then daily for 14 days; morbidity and mortality: twice daily; individual body weights: recorded on day 0 (the day of dosing) and on days 7 and 14- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities recorded. No tissues were retained.

Statistics:

No statistical analysis performed.

Results and discussion

Preliminary study:

Dose level - 300 mg/kg:- Mortality: there was no mortality.- Clinical observations: no signs of systemic toxicity were noted during the observation period.- Body weight: the animal showed expected gains in body weight over the observation period.- Necropsy: no abnormalities were noted at necrospy.

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 mg/kg bw

Based on:

act. ingr.

Mortality:

There were no deaths.

Clinical signs:

No signs of systemic toxicity were noted during the observation period.

Body weight:

All animals showed expected gains in body weight over the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (equivalent to greater than 1000 mg active ingredient/kg bw). Based on CLP Regulation, the substance is considered to not be classified.