Registration Dossier

Administrative data

Description of key information

The acute oral and dermal LD0 of 1,1-dimethylpropyl 1-methoxycyclohexyl peroxide are higher than 2000 mg/kg bw.

Oral route

The potential for oral toxicity of 1,1-dimethylpropyl 1-methoxycyclohexyl peroxide (Luperox XPS-TP) was evaluated using the Acute Toxic Class Determination following the OECD Guidelines no. 423 (Cerven, 2005a). Three healthy male and three healthy female Wistar albino rats were dosed orally with Luperox XPS-TP at 2000 mg/kg. The rats were observed 0.5, 1, 2, 3 and 4 hours postdose and once daily for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded immediately pretest, weekly and at termination. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination. All three male and three female animais survived the 2000 mg/kg oral dose. Instances of localized alopecia were the only abnormal physical signs noted during the observation period. Body weight changes were normal 5/6 animals. One female lost a slight amount of body weight between day 7 and day 14. Necropsy results revealed localized alopecia in two animals and darker than normal kidneys in 5/6 animals. One animal appeared normal during necropsy. The LD0 is > 2000 mg/kg.

Dermal route

The potential for toxicity of 1,1-dimethylpropyl 1-methoxycyclohexyl peroxide (Luperox XPS-TP) when applied dermally was evaluated following the OECD Guideline no. 402 (Gilotti, 2005b). Five healthy male and five healthy female Wistar Albino rats were dosed dermally with Luperox XPS-TP at 2000 mg/kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded at 24 hours postdose and on days 7 and 14. Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 hours postdose and once daily for 14 days. All animals were observed twice a day for mortality. Body weights were recorded pretest, weekly and at termination. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination. All ten animals survived the 2000 mg/kg dermal application. Instances of chromorhinorrhea were noted during exposure and instances of alopecia on the front limbs were noted during the study. Dermal effects were absent during the study. Body weight changes were normal in 8/10 animals. One female lost weight during the first week, but gained normally during the second week. Another female lost weight during the second week. Necropsy results revealed abnormalities of the kidneys in 7/10 animals and alopecia was noted in 2 females. The dermal LD0 is higher than 2000 mg/kg of body weight.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ace Animais, Boyertown, PA
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 366 - 397 grams for males and 241 - 273 grams for females
- Fasting period before study: yes
- Housing: in suspended wire mesh cages; 5/sex/cage prier to dosing and 3/sex/cage following dosing
- Diet: Fresh PMI Rat Chow, ad libitum
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.08 ml/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Animals were observed at 1/2, 1, 2, 3 & 4 hours post-dose and once daily thereafter for 14 consecutive days for mortality, toxicity & pharmacological effects.
Body Weights were recorded immediately pretest, weekly and at death or study termination in the survivors.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no mortality
Mortality:
Ali three male and three female animais survived the 2000 mg/kg oral dose.
Clinical signs:
Instances of localized alopecia were the only abnormal physical signs noted during the observation period.
Body weight:
Body weight changes were normal 516 animals. One female lost a slight amount of body weight
between day 7 and day 14.
Gross pathology:
Necropsy results revealed localized alopecia in two. animais and darker than normal kidneys in 5/6
animais. One animal appeared normal during necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD0 is > 2000 mg/kg.
Executive summary:

The potential for oral toxicity of Luperox XPS-TP was evaluated using the Acute Toxic Class Determinationfollowing the OECD Guidelines no. 423. Three healthy male and three healthy female Wistar albino rats were dosed orally with Luperox XPS-TP at 2000 mg/kg. The rats were observed 0.5, 1, 2, 3 and 4 hours postdose and once daily for 14 days for mortality, toxicity and pharmacological effects. Body weights were recorded immediately pretest, weekly and at termination. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination. All three male and three female animais survived the 2000 mg/kg oral dose. Instances of localized alopecia were the only abnormal physical signs noted during the observation period. Body weight changes were normal 5/6 animals. One female lost a slight amount of body weight between day 7 and day 14. Necropsy results revealed localized alopecia in two animals and darker than normal kidneys in 5/6 animals. One animal appeared normal during necropsy. The LD0 is > 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ace Animais, Boyertown, PA
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 229 - 280 g for males and 199 - 280 g for females.
- Fasting period before study: yes
- Housing: in suspended wire mesh cages; 1/cage
- Diet: Fresh PMI Rat Chow, ad libitum
- Water: ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 4 x 6 cm
- Type of wrap if used:The torso was wrapped with plastic in a semi-occlusive manner and was secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):Residual test article was removed by gently washing with distilled water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.08 ml/kg
Duration of exposure:
24 hours
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:
Animals were observed at 1/2, 1, 2, 3 & 4 hours post-dose and once daily thereafter for 14 consecutive days for mortality, toxicity & pharmacological effects.
Body Weights were recorded immediately pretest, weekly and at death or study termination in the survivors.
The test sites were scored for dermal irritation at 24 hours postdose and on days 7 and 14.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality
Mortality:
Ali ten animais survived the 2000 mg/kg dermal application.
Clinical signs:
Instances of chromorhinorrhea were noted during exposure and instances of alopecia on the front limbs were noted during the study.
Body weight:
Body weight changes were normal in 8/1 O animais. One female lost weight du ring the first week, but gained normally during the second week. Another female lost weight during the second week.
Gross pathology:
Necropsy results revealed abnormalities of the kidneys in 7/10 animais and alopecia was noted in 2 females.
Other findings:
Dermal effects were absent during the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD0 of Luperox XPS-TP is >= 2000 mg/kg of body weight.
Executive summary:

The potential for toxicity of Luperox XPS-TP when applied dermally was evaluated following the OECD Guidelineno. 402. Five healthy male and five healthy female Wistar Albino rats were dosed dermally with Luperox XPS-TP at 2000 mg/kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded at 24 hours postdose and on days 7 and 14. Animals were observed for toxicity and pharmacological effects at 1, 2 and 4 hours postdose and once daily for 14 days. All animals were observed twice a day for mortality. Body weights were recorded pretest, weekly and at termination. All animals were examined for gross pathology. Abnormal tissues were preserved in 10% neutral buffered formalin for possible future histological examination. All ten animals survived the 2000 mg/kg dermal application. Instances of chromorhinorrhea were noted during exposure and instances of alopecia on the front limbs were noted during the study. Dermal effects were absent during the study. Body weight changes were normal in 8/10 animals. One female lost weight during the first week, but gained normally during the second week. Another female lost weight during the second week. Necropsy results revealed abnormalities of the kidneys in 7/10 animals and alopecia was noted in 2 females. The dermal LD0 of Luperox XPS-TP is higher than 2000 mg/kg of body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

No classification is warranted according to CLP/GHS criteria.