Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 September 2012 to 25 March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Fully GLP compliant and in accordance with current test guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Viscous semi-solid
Details on test material:
Name: TOFA_TETA_PAA_BADGE_CGE_Adduct
CAS number: 186321-96-0
Batch number: WA520
Purity: 100%
Expiry date: 28 Feb 2014
Receipt date: 03 Sep 2012
Storage: stored in a sealed container, at room temperature, in the dark.

Test animals

Species:
rat
Strain:
other: HsdHan:WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: 248 to 286 g (males) and 173 to 199 g (females)
- Fasting period before study: Not applicable
- Housing: During the acclimatisation period, up to five rats of the same sex were accommodated in cages that conformed to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), each rat was individually housed in a similar cage. After completion of the Day 3 observations animals allocated to the main study were returned to group housing.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, ad libitum
- Water (e.g. ad libitum): Mains water, ad libitum
- Acclimation period: 7 to 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): The animal rooms were designed to permit 15 to 20 air changes per hour.
- Photoperiod (hrs dark / hrs light): The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

IN-LIFE DATES: From: 01 October 2012 To: 23 October 2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsum
- % coverage: 10%
- Type of wrap if used: Dense gauze patch retained in place by an elasicated, open-weave adhesive compression bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dermal test site of each rat was lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: Not applicable
Duration of exposure:
15 Days
Doses:
1 dose at 2000 mg/kg
No. of animals per sex per dose:
five male and five female rats was subjected to single dermal application of the test article at 2000 mg/kg. This group consisted of the two animals used in the preliminary test plus a further four male and four female rats to give the required group size of five males and five females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Clinical signs were recorded immediately post dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Individual records of clinical signs were maintained for each treated rat.
Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal reactions, necropsy findings
Statistics:
Not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no clinical signs of reaction to treatment.
Body weight:
One female showed no change in body weight during the first week of the study and another female showed a slight loss in body weight during the second week. All other rats gained weight during the first and second weeks of the study.
Gross pathology:
Abnormalities noted at necropsy were confined to a sore appearance of the skin at the treatment site.
Other findings:
No evidence of oedema was noted during the study period.
Very slight to well-defined erythema was noted in all males on Day 2. Very slight erythema persisted in one male to the end of the study and was also noted in one other male on Days 5 and 6.
Very slight erythema was noted in all females on Day 2. Very slight erythema was noted in one female on Days 3 and 4, with very slight to well-defined erythema noted in all females on Days 5, 6 and 7. Very slight erythema persisted in four females up to Day 14 and in one female on Day 15.
Other adverse dermal reactions noted were brown discolouration of the skin, shiny skin and scabbing.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute median lethal dermal dose of TOFA_TETA_PAA_BADGE_CGE_Adduct to rats was found to exceed 2000 mg/kg.
The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
Executive summary:

This study was conducted to determine the acute dermal toxicity of the test article, TOFA_TETA_PAA_BADGE_CGE_Adduct following a single (24 hour) semi-occluded topical application to the rat.

The test article was applied as an undiluted liquid to the clipped dorsum of a group of five male and five female rats on Day 1. Each rat received a single topical application at a dose level of 2000 mg/kg. The treated areas of dorsum were covered by a semi-occlusive dressing for 24 hours. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths and no clinical signs of reaction to treatment.

Adverse dermal reactions noted were very slight to well-defined erythema, brown discolouration of the skin, shiny skin and scabbing.

One female showed no change in body weight during the first week of the study and another female showed a slight loss in body weight during the second week. All other rats gained weight during the first and second weeks of the study.

Abnormalities noted at necropsy were confined to a sore appearance of the skin at the treatment site.

The acute median lethal dermal dose of TOFA_TETA_PAA_BADGE_CGE_Adduct to rats was found to exceed 2000 mg/kg.

The test material was considered to have no significant acute toxic risk in respect of its acute dermal toxicity and did not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).