Bis(3,5,5-trimethylhexanoyl) peroxide

Endpoint summary

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

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 or test system 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:

other: 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

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

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 or test system 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:

other: no clinical signs and no cutaneous reactions during study

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.