Registration Dossier

Administrative data

Description of key information

The oral LD50 is > 2000 mg/kg bw. No mortalities occurred and no signs of systemic toxicity were observed during the 14-day observation period. There are no key studies available for the inhalation or the dermal route.

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:
14 October 1992 - 6 November 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study is performed according to OECD guidelines and GLP.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral 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: Charles River (U.K.) Limited, Margate, Kent, England
- Age at study initiation:5 weeks
- Weight at study initiation: males from 116 - 138 g and for females from 116 - 131 g.
- Fasting period before study: removal of food for approximately 18 hours before administration of the test material.
- Housing: The animals were housed in stainless steel grid cages (Stephen Clark Fabrications Limited, Alva, Clackmannanshire, Scotland).
- Diet (e.g. ad libitum):ad libitum, commercially-available complete pelleted rodent diet (RM-1 S.Q.C., from Special Diets Services Limited, Witham, Essex, England)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 38-57
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: 14 October 1992 - 6 November 1992
Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200mg/ml
- Amount of vehicle (if gavage): 10ml/kg

DOSAGE PREPARATION (if unusual): The dosage was calculated and expressed gravimetrically in terms of the material as received. A fresh formulation of the test material was prepared shortly before administration and any surplus remaining after dosing was destroyed on the same day
Doses:
2000 mg/kg bw
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: Three separate inspections were made during the first hour after dosing and two further inspections during the remainder of Day 1. From Day 2 onwards the animals were inspected twice daily (morning and afternoon). The type t time of onset and duration of reactions to treatment were recorded. The bodyweight of each animal was recorded on the day before dosing and on Days It 8 and 15. The test was terminated on the morning of Day 15
- Necropsy of survivors performed: yes
Statistics:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities
Mortality:
There was no death.
Clinical signs:
There was no sign of reaction to treatment.
Body weight:
The animals achieved expected bodyweight gains.
Gross pathology:
Necropsy, on Day 15, revealed no significant macroscopic lesion.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 2000 mg/kg bw.
Executive summary:

The acute oral toxicity was investigated in a group of five male and five female CD rats at a dosage of 2000 mg/kg. The animals were starved overnight prior to dosing and the test material was administered at a constant volume-dosage of 10 ml/kg in maize oil. Mortality and signs of reaction to treatment were recorded during a subsequent 14-day observation period. The animals were killed on the following day and subjected to necropsy. There was no death and no sign of reaction to treatment. The animals achieved expected bodyweight gains and necropsy

revealed no significant macroscopic lesion. Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Quality of whole database:
A K1 study is available, supported by a K2 study.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed pre-GLP and no guideline is mentioned. Very limited data is provided on the methods and results, only a 1 page summary. No data on test substance composition or purity. Full evaluation of the validity of this study is not possible.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The hair was clipped from the back of each rabbit. The skin was abraded for 1/2 of the rabbits in each group. The test material was applied to the backs in appropriate doses and the site of application was covered with gauze bandaging and occluded with Saran Wrap.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2325 to 2960 grams
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: no data
- Type of wrap if used: The site of application was covered with gauze bandaging and occluded with Saran Wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: no data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): no data
- Constant volume or concentration used: no data
- For solids, paste formed: no data

Duration of exposure:
24 hours
Doses:
1000, 2000, 4000, 8000 mg/kg bw
No. of animals per sex per dose:
1
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality on a daily basis, no data on body weight.
- Necropsy of survivors performed: no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 8 000 mg/kg bw
Based on:
test mat.
Mortality:
0
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
study cannot be used for classification
Conclusions:
The acute dermal toxicity in male and female albino rabbits would be greater than 8000 mg/kg bw.
Executive summary:

Eight New Zealand White rabbits, equally divided as to sex, weighing 2325 to 2960 grams were exposed. The hair was clipped from the back of each rabbit. The skin was abraded for 1/2 of the rabbits in each group. The test material was applied, as received, to the backs in doses of 1000, 2000, 4000, 8000 mg/kg bw. The site of application was covered with gauze bandaging and occluded with Saran Wrap.

The rabbits were observed for death at 24 hours and daily thereafter for a total of 14 days. None of the animals died, no other effects reported. The acute dermal toxicity in male and female albino rabbits would be greater than 8000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

The registered substance was not acutely toxic to rats when tested by the oral gavage route. Based on the pattern of use ingestion by humans is unlikely.

An acute toxicity study via the dermal route was not performed since this is scientifically unjustified, for details see above. A weight of evidence approach is scientifically applicable for chemically comparable organic peroxides and allows one to conclude also a dermal LD50 > 2000 mg/kg bw for the untested organic peroxide.

An acute toxicity study via the inhalation route was not performed and can be waived according to REACH Annex VIII since exposure via this route is unlikely.

Justification for selection of acute toxicity – oral endpoint

K1:The study is performed according to OECD guidelines and GLP. LD50 >2000 mg/kg bw, no mortalities occurred.

Justification for selection of acute toxicity – inhalation endpoint

In accordance with column 2 of REACH Annex VIII, the test for acute inhalation toxicity (required in section 8.5) does not need to be conducted. Testing by the inhalation route is not appropriate since exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to droplets of an inhalable size. The vapour pressure is very low (see section 4.6) and the pattern of use does not lead to the formation of droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint

Numerous organic peroxides have been tested in acute dermal toxicity tests (41 organic peroxides covering all chemical subgroups/families of organic peroxides, excluding hydroperoxides). Experimental data of all of these organic peroxides, (except hydroperoxides), show no toxic effects at dermal application up to the tested concentration limit of 2000 mg/kg bw and show for this reason an acute dermal toxicity of >2000 mg/kg bw. Therefore, a weight of evidence approach is scientifically applicable for chemically comparable organic peroxides and allows one to conclude also a dermal LD50 > 2000 mg/kg bw for the untested organic peroxide, supported by the 1976 test results.  Additional testing for such organic peroxides is therefore not required and would not be in line with animal welfare legislation.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study, the data is conclusive but not sufficient for classification.