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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 July 2011 - 02 March 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Stuy was conducted in accordance with International guidelines and in accordance with GLP. All guideline validity criteria were met.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Commission Regulation (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF, Test Data for Registration of Agricultural Chemicals, Acute dermal toxicity (2-1-2), 12 Nousan No 8147, Agricultural Production Bureau
Version / remarks:
24 November 2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid
EC Number:
813-120-0
Cas Number:
1262967-45-2
Molecular formula:
C21H36O8 C26H46O8 C31H56O8 C36H66O8 C41H76O8
IUPAC Name:
Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid
Test material form:
liquid
Specific details on test material used for the study:
RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity: N/A
- Specific activity: N/A
- Locations of the label: N/A
- Expiration date of radiochemical substance: N/A

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark and under nitrogen.
- Stability under test conditions: Asumed stable.
- Solubility and stability of the test substance in the solvent/vehicle: Applied as supplied.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: N/A.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: N/A
- Preliminary purification step (if any): N/A
- Final dilution of a dissolved solid, stock liquid or gel: N/A
- Final preparation of a solid: N/A

FORM AS APPLIED IN THE TEST (if different from that of starting material): Applied as supplied.

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable): N/A

OTHER SPECIFICS: No

Test animals

Species:
rat
Strain:
other: Crl:CD'SD'
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Chares River UK Ltd.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: Males: 339-365 g; Females: 215-250 g
- Fasting period before study: No
- Housing: The animals were allocated without conscious bias to cages within the treatment group. They were housed individually from Day -1 until Day 3 when they were returned to group housing (in groups of five rats of the same sex). The cages were solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 ºC
- Humidity (%): 40-70 %
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12:12 ligh: dark

IN-LIFE DATES: From: 17 August 2011 To: 31 August 2011

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 50x50 mm
- % coverage: 10 % body area
- Type of wrap if used: Covered with porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with warm water (30 - 40 °C), to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.02 mL/kg (specific gravity of test item = 0.992 g/mL)
- Concentration (if solution): N/A, applied as supplied.
- Constant volume or concentration used: Yes
- For solids, paste formed: N/A

VEHICLE
- Amount(s) applied (volume or weight with unit): N/A, applied as supplied (i.e. liquid)
- Concentration (if solution): N/A
- Lot/batch no. (if required): N/A
- Purity: N/A
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, dermal reactions, body weight, macroscopic pathology
Statistics:
Not required (no effect)

Results and discussion

Preliminary study:
N/A
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
There were no deaths.
Clinical signs:
There were no systemic response to treatment in any animal.
Body weight:
There was considered to be no overall adverse effect on bodyweight gain, however, low bodyweight gains / bodyweight stasis was observed for some individuals.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Any other information on results incl. tables

Table 3       Dermal reactions

 

Dose

(mg/kg)

Sex

Animal no.

E= erythema

O = oedema

Day 2-15

2000

Male

B1

E

0

O

0

B2

E

0

O

0

B3

E

0

O

0

B4

E

0

O

0

B5

E

0

O

0

Female

B6

E

0

O

0

B7

E

0

O

0

B8

E

0

O

0

B9

E

0

O

0

B10

E

0

O

0

Table 4       Individual bodyweight

 

Dose

(mg/kg)

Sex

Animal no.

Bodyweight (g) at Day

Bodyweight changes (g) at Days

1*

8

15

1-8

8-15

2000

Male

B1

339

385

422

46

37

B2

354

390

426

36

36

B3

365

382

416

17

34

B4

364

381

426

17

45

B5

348

377

413

29

36

Mean

354

383

421

-

-

Female

B6

250

257

262

7

5

B7

215

236

251

21

15

B8

247

247

264

0

17

B9

237

247

262

10

15

B10

232

239

251

7

12

Mean

236

245

258

-

-

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the dermal LD50 was established to exceed 2000 mg/kg bw in male and female Crl:CD'SD' strain rat.
Executive summary:

OECD 402 (2012) - In an acute dermal toxicity study, a group of 8-12 week old male (5 individuals) and female (5 individuals) (nulliparous) Crl:CD’SD’ rats were exposed to a single dermal application of Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid for 24 hours at a single dose rate of 2000 mg/kg bw (limit test).The test item was applied undiluted to a 50 x 50 mm contact area, equivalent to approximately 10 % of the body surface. After 24-hour exposure, the test site was cleaned with warm water and observations recorded for 14 days.

 

In the absence of mortality during the observation period, the oral LD50 was estimated to be greater than 2000 mg/kg bw.

 

In addition, there were no treatment related clinical signs, necropsy findings or changes in body weight observed in any of the individuals.

 

Tetraesters of pentaerythritol with 2-methylpropanoic acid and 3,5,5-trimethyl-hexanoic acid did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.