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Description of key information

Acute oral toxicity was assessed in a non GLP study equivalent to OECD 401. Acute dermal toxicity was assessed in a GLP guideline study according to OECD 402yt 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Valid with restriction; meets generally accepted scientific standards, well documented and acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: TNO
- Age at study initiation: young adults
- Weight at study initiation: males: 182-322 g, females: 140-230 g
- Fasting period before study: overnight
- Housing: goups of 5
- Diet (e.g. ad libitum): after treatment ad libitum
- Water (e.g. ad libitum): after treatment ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25°C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
75% solution in isododecane
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 20 ml per kg bodyweight
Doses:
11.6, 13.9, 16.7, and 20 ml per kg bodyweight
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: no data
- Necropsy of survivors performed: yes
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 12.7 mL/kg bw
Based on:
test mat.
95% CL:
>= 9.3 - <= 17.3
Mortality:
Mortality of the doses tested: 40-90 % (see Table 1); most death occured between 17 hours and 6 days after treatment; two males died on day 8 and 9
Clinical signs:
sluggishness, humpback behaviour and severe diarrhoea; irritation of the skin in the area around anus and tailroot, encrustations around eyes and nostrils; at the end of the observation period some rats showed necrosis of the skin around anus and tailroot
Body weight:
no data
Gross pathology:
no treatment-related gross alterations

Table 1: Dosis applied and mortality observed

Dose ml/kg

Mortality (No. of died per total animals per dose)

 

males

females

% of mortality

11.6

3/5

1/5

40

13.9

3/5

3/5

60

16.7

5/5

4/5

90

20

5/5

3/5

80

The LD50 was calculated according to the method of Weil (Biometrics 8 (1952) 249 -263).

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of bis-(3,5,5-trimethylhexanoyl)peroxide (75% in isododecane) was calculated to be 12.7 ml which equates to 11.96 g/kg bw.
Executive summary:

In an acute oral toxicity study, groups of fasted, young adult Wistar derived male and female rats (5 per sex and dose) were given a single oral dose of  bis-(3,5,5-trimethylhexanoyl)peroxide in 75% isododecane at doses of 11.6, 13.9, 16.7 and 20 ml/kg bw by gavage and were observed for 14 days. The LD50 was calculated to be 12.7 ml per kg body weight (which equates to 11.96 g/ kg bw) with 9.3 and 17.3 as the 95 % confidence limits.

Bis-3,5,5 -trimethylhexanoyl peroxide in 75% isododecane is practically non-toxic. This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study in the rat.

 

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-10-17 to 1995-10-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Credo, 69210 L`Arbresle, France
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: males 259 +/- 6 g, females 229 +/- 2 g
- Housing: during acclimatisation 4-7 of same sex; during treatment individually
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2°C
- Humidity (%): 30-70 %
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
the substance was administered in its original form
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 cm x 6 cm (females), 5 cm x 7 cm (males)
- % coverage: 10 %
- Type of wrap if used: hydrophilic gauze pad (Semes France)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.3 ml/kg
- Concentration (if solution): 99 %


Duration of exposure:
24 h
Doses:
2000 mg/kg
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: frequent observations during hours following administration; thereafter: at least once a day; weighing: before administration and on day 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
no statistics
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no death occured during obeservation period
Clinical signs:
no clinical signs and no cutaneous reactions during study
Body weight:
body weight gain was not influenced by treatment
Gross pathology:
no apparent abnormalities
Other findings:
none

Table 1: Individual and mean body weight and weekly body weight change of treated rats (g)

Dose (mg/kg)

Volume (ml/kg)

Sex

Animals

Day 1

Body weight gain

Day 8

Body weight gain

Day 15

2000

2.3

male

1

264

42

306

71

377

 

 

 

2

258

31

289

55

344

 

 

 

3

265

51

316

76

392

 

 

 

4

257

56

313

54

367

 

 

 

5

251

50

301

53

354

 

 

 

M

259

46

305

62

367

 

 

 

SD

6

10

11

11

19

2000

2.3

female

1

229

18

247

19

266

 

 

 

2

228

2

230

17

247

 

 

 

3

232

28

260

18

278

 

 

 

4

230

12

242

30

272

 

 

 

5

227

27

254

26

280

 

 

 

M

229

17

247

22

269

 

 

 

SD

2

11

12

6

13

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions the dermal LD0 of the test substance bis-(3,5,5-trimethylhexanoyl)peroxide was higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.
Executive summary:

The acute dermal toxicity of bis-(3,5,5-trimethylhexanoyl) peroxide was assessed according to OECD guideline 402. The test substance was applied in its original form to the skin of one group of ten Sprague-Dawley rats (five males and five females) at a dose of 2000 mg/kg. The test site was covered by a semi-occlusive dressing for 24 h. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single administration of the test substance. All animals were subject to necroscopy. No cutaneous reactions were observed. The behaviour and body weight was not affected by the treatment. No deaths occurred at 2000 mg/kg. No abnormalities were observed at necroscopy.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

The LD50 of bis-(3,5,5-trimethylhexanoyl)peroxide (75% in isododecane) was calculated to be 12.7 ml which equates to 11.96 g/kg bw. The dermal LD50 of bis-(3,5,5-trimethylhexanoyl)peroxide is higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.


Justification for selection of acute toxicity – oral endpoint
study is equivalent to a guideline study

Justification for selection of acute toxicity – dermal endpoint
GLP guideline study

Justification for classification or non-classification

LD50 values for oral and dermal acute toxicity were above the limit dose of 2000 mg/kg bw.