Reaction products of tetraethylenepentamine and maleic anhydride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-01-14 to 2015-01-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented study performed according to OECD 402 and EU Method B.3 guideline, in compliance with GLP. No deviations were noted.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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- Analytical purity: 50 %- Purity test date: no data- Lot/batch No.: BLW0010057- Expiration date of the lot/batch: 2015-12-01- Stability under test conditions: no data- Storage condition of test material: at approximately 4°C in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: 5 male and 5 female Wistar strain rats, RccHan(TM): WIST, supplied by Harlan Laboratories UK Ltd., Oxon, UK. - Age at start of study: 8-12 weeks- Weight at start of the study (day 0): 234 - 272 grams for males, 207 - 223 grams for females - Fasting period before study: no data- Housing: in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. - 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, free access to mains drinking water- 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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE- Area of exposure: back and flanks of the animals, clipped free of hair- % coverage: approximately 10% of total body surface area- Type of wrap if used: the test item was applied using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. REMOVAL OF TEST SUBSTANCE- Washing (if done): the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test item.- Time after start of exposure: 24 hoursTEST MATERIAL- Amount(s) applied (volume or weight with unit): 3.37 ml/kg- Concentration (if solution): no data- Constant volume or concentration used: yesVEHICLE- no vehicle used

Duration of exposure:

24 hours

Doses:

4000 mg/kg (equivalent to 2000 mg active ingredient/kg body weight)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days- Frequency of observations and weighing: mortality/overt signs: 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days; clinical signs: after removal of the dressings and subsequently once daily for 14 days. The test sites were examined for evidence of primary irritation (erythema and eschar formation and oedema formation). Any other skin reactions were also recorded; individual body weights were recorded prior to application of the test item on day 0 and on days 7 and 14.- Necropsy of survivors performed: yes, at the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necrposy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopical abnormalities was recorded. No tissues were retained.

Statistics:

No statistical analysis performed.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 2000 mg active ingredient/kg bw

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 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. There were no signs of dermal irritation.

Body weight:

Animals showed expected gains in body weight, except for two females which showed body weight loss during the first week but expected gain in body weight during the second week.

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 acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 4000 mg/kg body weight (equivalent to 2000 mg active ingredient/kg body weight). Based on the CLP Regulation, the test item is considered not to be classified for acute dermal toxicity.