Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trigonox 36-CD 75 (bis(3,5,5-trimethylhexanoyl peroxide)
- Substance type: organic peroxide
- Physical state: clear colourless liquid
- Analytical purity: 75 % in isododecane
- Storage condition of test material: -20°C

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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

Any other information on results incl. tables

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).

Applicant's summary and conclusion

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.