1,2,3,4-Butanetetracarboxylic acid, tetramethyl ester, reaction products with 1,2,2,6,6-pentamethyl-4-piperidinol and β,β,β',β'-tetramethyl-2,4,8,10-tetraoxaspiro[5.5]undecane-3,9-diethanol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 Dec 2016 - 04 Jan 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Rats are the preferred species of choice as historically used for safety evaluation studies and are specified in the appropriate test guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

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:

fixed dose procedure

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 112Z5
- Purity: 100%
- Physical state/ Appearance: white powder
- Expiration date: 30 Jun 2017
- Storage condition of test material: room temperature 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: Envigo RMS (UK) Limited, Oxon, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: at least 200g
- Housing: suspended solid floor polypropelene cages furnished with woodflakes
- Diet: ad libitum:
- Water (e.g. ad libitum):
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/ 12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: 10% of the total body surface area
- Type of wrap if used: self adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin wipe with cotton wool moistened with arachis oil BP
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg

Duration of exposure:

24h

Doses:

2000mg/kg

No. of animals per sex per dose:

5 males at 2000mg/kg
5 females at 2000mg/kg

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14days
- Frequency of observations: 30min, 1h, 2h and 4h after dosing and subsequently once daily for 14 days.


- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
- all animals showed expected gains in body weights

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No deaths

Clinical signs:

There were no signs of systematic toxicity during the observation period

Body weight:

All animals showed expected gains in weight

Gross pathology:

No abnormalities were noted during necropsy.

Other findings:

Very slight erythema was noted at the test sites of alll animals.
Very slight edema was also noted at the test of all males and four females.
No abnormalities were noted at necropsy

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test itiem in the Wistar strain rat was found to be greater than 2000mg/kg body weight