3,7-bis(diethylamino)phenoxazin-5-ium acetate

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Remarks:

Combined repeated dose repro-devp. Screen

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source.

Data source

Reference

Reference Type:

secondary source

Title:

combined repeated-dose/reproductive/developmental toxicity screening test for Di-tert-butyl Peroxide

Author:

SIDS INITIAL ASSESSMENT PROFILE

Year:

2012

Bibliographic source:

combined repeated-dose/reproductive/developmental toxicity screening test for Di-tert-butyl Peroxide OECD SIDS COCAM 3 16-18 October 2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

To evaluate the oral repeated dose toxicity of Di-tert-butyl Peroxide in rats by Combined repeated dose repro-devp. Screening test.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Di-tert-butyl peroxide

EC Number:

203-733-6

EC Name:

Di-tert-butyl peroxide

Cas Number:

110-05-4

Molecular formula:

C8H18O2

IUPAC Name:

2,2'-dioxybis(2-methylpropane)

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): bis(1,1-dimethylethyl)peroxide
- IUPAC name: 2,2'-dioxybis(2-methylpropane)
- Molecular formula (if other than submission substance): C8H18O2
- Molecular weight (if other than submission substance): 146.2282
- Smiles notation (if other than submission substance): C(OOC(C)(C)C)(C)(C)C
- InChl (if other than submission substance): 1S/C8H18O2/c1-7(2,3)9-10-8(4,5)6/h1-6H3
- Substance type: Organic
- Physical state: Liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): bis(1,1-dimethylethyl)peroxide
- IUPAC name: 2,2'-dioxybis(2-methylpropane)
- Molecular formula (if other than submission substance): C8H18O2
- Molecular weight (if other than submission substance): 146.2282
- Smiles notation (if other than submission substance): C(OOC(C)(C)C)(C)(C)C
- InChl (if other than submission substance): 1S/C8H18O2/c1-7(2,3)9-10-8(4,5)6/h1-6H3
- Substance type: Organic
- Physical state: Liquid

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

not specified

Vehicle:

not specified

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

>42 days for female
42 days Male

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

0, 100, 300 or 1000 mg/kg-bw/day

No. of animals per sex per dose:

Total no of animals 80
0 mg/kg/day -10 male and 10 female
100 mg/kg/day-10 male and 10 female
300 mg/kg/day-10 male and 10 female
1000 mg/kg/day -10 male and 10 female

Control animals:

yes, concurrent vehicle

Details on study design:

Not specified.

Examinations

Observations and examinations performed and frequency:

Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Not specified

DETAILED CLINICAL OBSERVATIONS: Not specified

BODY WEIGHT: Not specified

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified

HAEMATOLOGY: Not specified

CLINICAL CHEMISTRY: Not specified

URINALYSIS: Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified

Sacrifice and pathology:

Sacrifice and pathology
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

Not specified.

Statistics:

Not specified.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Increased relative weights; minimal centrilobular and diffuse hepatocellular hypertrophy in liver; moderate diffuse tubular degeneration/regeneration with slight multifocal single cell necrosis and hyaline casts as well as hyaline droplets in kidneys of males was observed at 1000 mg/kg bw/day in treated animal compare to control.

At 300 mg/kg bw/day increased relative liver and kidney weights were observed in treated males and females rats compare to control.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

100 other: mg/kg/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

Remarks on result:

other: No toxic effect were observed

Target system / organ toxicity

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL was considered to be 100 mg/kg/day in male and female rats for Di-tert-butyl Peroxide(110-05-4) by Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test.

Executive summary:

Repeated dose toxicity study was assessed for Di-tert-butyl Peroxide for its possible repeated dose toxicity effect. For this purpose Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test was performed according to OECD Guideline 422.The test material was exposed to the male and female rats by oral gavage for subchronic period. The test material was used at the concentration of0, 100, 300 or 1000 mg/kg/day.

Increased relative weights; minimal centrilobular and diffuse hepatocellular hypertrophy in liver; moderate diffuse tubular degeneration/regeneration with slight multifocal single cell necrosis and hyaline casts as well as hyaline droplets in kidneys of males was observed at 1000 mg/kg bw/day in treated animal compare to control.

At 300 mg/kg bw/day increased relative liver and kidney weights were observed in treated males and females rats compare to control.

Therefore NOAEL was considered to be 100 mg/kg/day in male and female rats for Di-tert-butyl Peroxide by Oral gavage for sub chronic study.