Registration Dossier

Administrative data

Description of key information

The registered substance, ±70% in phlegmatizer, was not acutely toxic to rats when tested by the oral gavage route. The oral LD50 is > 5000 mg/kg bw. No mortalities occurred and no signs of systemic toxicity were observed during the 14-day observation period. Based on the pattern of use ingestion by humans is unlikely.

An acute toxicity study via the dermal route was not performed with the registered substance since this is scientifically unjustified. 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.

Numerous organic peroxides, from different organic peroxide categories defined by chemical structure, have been tested in acute dermal toxicity tests (+/- 35 organic peroxides covering all chemical subgroups/families of organic peroxides (dialkyl peroxides, diacyl peroxides, peroxymonocarbonates, ketine peroxides, peroxydicarbonates and peroxyketals)). Experimental data of all of these organic peroxides, 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. 

In this dossier the robust study summaries are included for the closest related substances belonging to the family of peroxyesters. CAS 26748-41-4, 29240-12-3, 13122-18-4, 22288-41-1. As described above for these four substances the dermal LD50 is >2000 mg/kg bw/d. Based on these data it is concluded that the dermal LD50 for the registered substance is also >2000 mg/kg bw/d.

Additional testing for the registered substance is therefore not required and would not be in line with animal welfare legislation.

There are no studies available for the inhalation route. 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.

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:
21 May 1986 - 11 June 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was 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:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, Brussels, Belgium. Date of arrival at the animal house
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: The body weights of the males on day 0 ranged from 304 to 332 g and those of the females from 200 to 247 g.
- Fasting period before study: Feed was withheld overnight before dosing till approximately 4 hours after administration of the test substance
- Housing: individually housed in polycarbonate cages
- Diet (e.g. ad libitum): ad libitum (standard laboratory animal diet (RMH-B, pellet diameter 10 mm))
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 50-95
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 21 May 1986 - 11 June 1986
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
The test substance was administered as a single dose using a stainless steel stomach cannula. Prior to dosing the test substance was removed from storage and was kept on ice until dosing. The dose volume was 5.7 ml/kg body weight. The day of dosing was considered as day 0.
Doses:
5000 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: Cage-side observations were performed on the day of dosing (approximately once every two hours) and daily thereafter. With exception of weekends and holidays a mortality check was performed at the end of the day. Individual body weights (with group means and standard deviation) were measured weekly. At the end of the study (day 14) all surviving animals were sacrificed by CO2-asphyxation and subjected to autopsy.
- Necropsy of survivors performed: yes
- Other examinations performed: None
Statistics:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occurred.
Clinical signs:
No signs of systemic toxicity were observed during the 14-day observation period.
Body weight:
Weekly group mean body weight gain was normal. There was no evident sex related effect.
Gross pathology:
Macroscopic examination of all animals at the end of the study revealed no test substance related gross abnormalities.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 5000 mg/kg bw
Executive summary:

One group of Wistar rats, comprising 5 males and 5 females, received a single oral dose of the test substance 5000 mg/kg body weight. No mortalities occurred and no signs of systemic toxicity were observed during the 14-day observation period. Weekly group mean body weight gain was normal. There was no evident sex related effect. Macroscopic examination of all animals at the end of the study revealed no test substance related gross abnormalities. Since no mortalities occurred, the LD50 value for males and females combined was estimated to exceed 5.0 g/kg body weight.

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

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 adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-06-24 to 1998-07-08
Reliability:
1 (reliable without restriction)
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1992
Deviations:
no
Principles of method if other than guideline:
NA
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Crédo, 69210 L'Arbresle, France
- Age and Weight at study initiation: On the day of treatment, the animals were approximately 8 weeks old, and had a mean body weight ± standard deviation of 255 ± 3 g for the males and 222 ± 11 g for the females.
- Fasting period before study:
- Housing: During the acclimatization period, four to seven animals of the same sex were housed in polycarbonate cages (48 cm x 27 cm x 20 cm). During the treatment period, the animals were housed individually in polycarbonate cages (35.5 cm x 23.5 cm x 19.3 cm)
- Diet (e.g. ad libitum): All the animals had free access to A04 C pelleted diet (UAR, 91360 Villemoisson-sur-Orge, France).
- Water (e.g. ad libitum): Drinking water filtered by FG Millipore membrane (0.22 micron) was provided ad libitum
- Acclimatization: at least 5 days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2°C
- Humidity (%): 30 to 70 %
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h light/ 12 h dark
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: females: 5 cm x 6 cm; males: 5 cm x 7 cm
- % coverage: approximately 10 %
- Type of wrap if used: A hydrophilic gauze pad was applied to the skin. The test substance and the gauze pad were held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: At least once a day until day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not performed
Preliminary study:
NA
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No death occurred during the study
Clinical signs:
No clinical signs and no cutaneous reactions were observed during the study.
Body weight:
The body weight gain of one female was reduced between day 1 and 15 and another female lost weight during this sample period. The overall body weight gain of the other animals was not affected by treatment with the test substance.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
NA

No remarks

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions, the dermal LD0 of the test substance tert-Butylperoxy-3,5,5-trimethylhexanoat is equal to or higher than 2000 mg/kg in rats.
Executive summary:

Tert-Butylperoxy-3,5,5-trimethylhexanoat was tested in a single dermal application to rats. The application was performed with the undiluted test substance at the dose of 2000 mg/kg, taking into consideration that its specific gravity was 0.89. The test site was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test substance. All animals were subjected to necropsy.

No death occurred at 2000 mg/kg. No clinical signs were observed. The body weight gain of one female was reduced between day 1 and 15 and another female lost weight during this same period. The overall body gain of the other animals was not affected by treatment with the test substance. No cutaneous reactions were observed. No apparent abnormalities were observed at necropsy.

Under these experimental conditions, the dermal LD0 of the test substance tert-Butylperoxy-3,5,5-trimethylhexanoat is equal to or higher than 2000 mg/kg in rats.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Apparently well conducted study.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Two females were excluded from interpretation, as it was concluded that exposure to the test substance had been inadequate in these animals due to slipping of the bandages from the application area during the exposure period.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Conditions
Air-conditioned room with approximately 15 air changes per hour and the
environment controlled with optimal conditions considered as being a temperature
of 21'C and a relative humidity of 50%. Fluctuations from these optimal
conditions were noted, but were considered not to have affected study integrity.
Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.

Accommodation
Individually housed in labelled polycarbonate cages containing purified sawdust
as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands).
Certificates of analysis were examined and then retained in the NOTOX archives.
Acclimatisation period was at least 5 days before start of treatment under
laboratory conditions.

Diet
Free access to standard pelleted laboratory animal diet (from Carfil Quality
BVBA, Oud-Turnhout, Belgium). Certificates of analysis were examined and then
retained in the NOTOX archives.

Water
Free access to tap-water. Certificates of quarterly analysis were examined and
then retained in the NOTOX archives.
Type of coverage:
other: The test substance wasA dressing, consisting of a surgical gauze patch , successively covered with aluminium foil,and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandagesin females only.
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day before exposure (day -i) an area of approximately
5x7 cm on the back of the animal was clipped.

The test substance was applied in an area of approx. 10%
of the total body surface, i.e. approx. 25 cm2 for males
and 18 cm2 for females. The test substance was held in
contact with the skiQ with a dressing, consisting of a
surgical gauze patch , s~ccessively covered with
aluminium fOil,and Coban flexible bandage. A piece of
Micropore tape was additionally used for fixation of the
bandages in females only.

Frequency: Single dosage, on day 1.
Dose level: 2000 mg/kg (2.25 ml/kg) body weight.
Dose volume calculated as follows: dose level: density.

Duration of exposure:
24 hours, after which dressings were removed and the skin
cleaned of residual test substance using water.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 per sex
Control animals:
not required
Details on study design:
Mortality/Viability: twice daily

Body weights: Days 1 (pre-administration), 8 and 15.

Clinical signs: At periodic intervals on the day of dosing (day 1) and
once daily thereafter, until day 15. The time of onset,
degree and duration were recorded and the symptoms graded
according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).

Necropsy: At the end of the observation period, all animals were
sacrificed by asphyxiation using an oxygen/carbon dioxide
procedure and subjected to necropsy. Descriptions of all
internal macroscopic abnormalities were recorded.
Statistics:
None
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred
Clinical signs:
Red staining in the neck was observed from day 2 onwards in one female and from
day 10 onwards in another and persisted until termination in both animals.
Erythema and scales were seen in the treated skin-area among the majority of
animals. The animals had recovered from these symptoms between days 3 and 9. An
incidental observation of scabs was recorded on day 11 for one male. Scabs in
the treated skin-area were also seen in another male from day 11 onwards until
termination.
Yellow staining (on the back and flank) and red staining (on the flank and
abdomen) was noted among the majority of animals during the course of the study.
Yellow staining persisted until termination in all of these animals. It was
considered that the staining was caused by remnants of the test substance,
despite its colourless appearance.
Body weight:
The changes noted in body weight gain in males and females were within the range
expected for rats used in this type of study and were therefore considered not
indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the
animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of 1,1,3,3-TETRAMETHYLBUTYLPEROXY PIVALATE in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Assessment of acute dermal toxicity with 1,1,3,3-TETRAMETHYLBUTYLPEROXY PIVALATE in the rat. The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, Part B.3, 'Acute Toxicity-Dermal' and OECD No.402, 'Acute Dermal Toxicity'. 1,1,3,3-TETRAMETHYLBUTYLPEROXY PIVALATE was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). Two females were excluded from interpretation, as it was concluded that exposure to the test substance had been inadequate in these animals due to slipping of the bandages from the application area during the exposure period. Since no mortality or severe signs of toxicity were observed in the other animals, no additional animals were treated for replacement. It was considered that the conclusion and integrity of the study was not affected by the exclusion of two females (and using the three remaining females only). No mortality occurred. Red staining in the neck was observed from day 2 onwards in one female and from day 10 onwards in another and persisted until termination in both animals. Erythema and scales were seen in the treated skin-area among the majority of animals. The animals had recovered from these symptoms between days 3 and 9. An incidental observation of scabs was recorded on day 11 for one male. Scabs in the treated skin-area were also seen in another male from day 11 onwards until termination. Yellow staining (on the back and flank) and red staining (on the flank and abdomen) was noted among the majority of animals during the course of the study. Yellow staining persisted until termination in all of these animals. It was considered that the staining was caused by remnants of the test substance, despite its colourless appearance. The mean body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of 1,1,3,3-TETRAMETHYLBUTYLPEROXY PIVALATE in Wistar rats was established to exceed 2000 mg/kg body weight.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
, number of animals per sex and dose, dose levels examined, no necropsy of the survivers
GLP compliance:
no
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
- Weight at study initiation: 2374 to 2776 gr.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
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 appropriate doses. the site of application was covered with gause bandaging and occluded with saran wrap.
Duration of exposure:
24 hours
Doses:
1000, 2000, 4000, 8000 mg/ kg bw
No. of animals per sex per dose:
2 animals of one sex were used for each dose level
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight, organ weights
Sex:
male/female
Dose descriptor:
LD0
Effect level:
8 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 8 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality was observed
Clinical signs:
Not indicated
Body weight:
All rabbits exhibited body weight gains or maintained their body weight during the14 day observation period
Gross pathology:
Not performed as all animals survived
Interpretation of results:
GHS criteria not met
Conclusions:
A LD50 value of > 8000 mg/kg bw was determined in the study for the test substance 75 % t-butyl peroxyneodecacnoate in solvent. A LD50 value of > 6000 mg/kg bw was calculated for 100 % t-butyl peroxyneodecanoate.
Executive summary:

The test substance 75 % t-butyl peroxyneodecanoate in mineral spirits was examined for its acute dermal toxicity, similar to an OECD no. 402 study guideline. Eight New Zealand white rabbits were equally divided to sex and to 4 dosage groups of 1000, 2000, 4000, and 8000 mg/kg bw. The hair was clipped from the back of each rabbit, the test substance was applied for 24 hours, as received to the backs in appropriate doses and the application site was covered with gauze bandaging and occluded with saran wrap.

After observation time of 14 days no mortality was observed and all rabbits exhibited body weight gains or maintained their body weight during the 14 day observation period. Thus, the deduced LD0 and LD50 values and are 8000 mg/kg bw and > 8000 mg/kg bw respectively. A LD50 value of > 6000 mg/ kg bw is calculated for 100 % t-butyl peroxyneodecanoate.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Date: September 24, 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to
Guideline:
other: Conducted in accordance with the regulations for Good Laboratory Practices as described by the FDA (21 CFR Part 58) and FDRL Standard Operating Procedures.
GLP compliance:
yes
Test type:
standard acute method
Specific details on test material used for the study:
FDRL Test Article ID: 81-0558
Sponsor Test Article ID: TA-54M75; tert-amyl peroxypivalate 75% in odorless mineral spirit
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Five male and 5 female adult New Zealand White rabbits, weighing between 2.0 and 4.0 kg, were purchased from H.A.R.E. - Rabbits for Research, Hewitt, N.J. for use in this-study. H.A.R.E. - Rabbits is a USDA approved supplier.
All animals were acclimated a minimum of 5 days. During this acclimation period, the rabbits were examined with respect to their general health to assure their suitability as test animals. The rabbits were housed individually
in wire mesh bottom cages. NIH Animal Feed A (certified) and water were provided ad libitum. Animals were identified by use of ear tags and cage cards.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The back and flanks of each rabbit were clipped free of fur with electrical clippers not more than 24 hours before study initiation. The clipped area constituted approximately 30 percent of the total body surface.
On the day of testing and just prior to the application of the test article, abrasion of the skin was performed on the exposure sites of 3 males and 2 female rabbits. The skin of the remaining 2 male and 3 female rabbits was left intact. Abrasions were made with the point of a 22 gauge disposable hypodermic needle. The abrasions were minor incisions through the stratum corneurn that were not sufficiently deep enough to disturb the derma or to produce bleeding.
The test article was administered under an occlusive binder at a level of 2.0 g/kg. The occlusive binder consisted of a layer of plastic wrap, a protective cloth and stockinette binder, all securely held in place with masking tape. The occlusive binder is applied to maintain contact and minimize evaporation of the applied test article.
If the test article was solid, it was moistened with physiological saline, (1 ml saline per 1 g of test article) before dermal application. Liquid test articles are administered as received.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
no
Details on study design:
After an exposure period of 24 hours the occlusive binders were-removed. The exposure sites were then gently wiped with clean gauze to remove as much nonabsorbed test article as possible. Observations for mortality, local reactions, and toxicological findings were recorded for a total of 14 days. Body weights were recorded on the initial day of testing, day 8 and at study termination or day of death.
Only those animals that died during the progress of the study were subjected to a gross necropsy.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
95% CL:
>= 0 - <= 40
Mortality:
1 in 10 rabbits (10% mortality)

Table 1 Dosing schedule

Animal Number and Sex

Body Weight (g) at Day

Dosage level

g/kg

Dose

ml (Total)

1

8

15

WAD

001m

2.46kg

2.52kg

2.58kg

 

2.00 g/kg

5.29

002m

2.38kg

2.50kg

2.40kg

 

2.00 g/kg

5.12

003m

2.74kg

2.49kg

2.57kg

 

2.00 g/kg

5.89

004m

2.72kg

2.73kg

2.86kg

 

2.00 g/kg

5.85

005m

2.87kg

2.93kg

3.10kg

 

2.00 g/kg

6.17

006f

2.86kg

2.34kg

2.60kg

 

2.00 g/kg

6.15

007f

2.14kg

2.21kg

2.50kg

 

2.00 g/kg

4.60

008f

2.52kg

2.35kg

2.68kg

 

2.00 g/kg

5.42

009f

2.60kg

2.61kg

-

2.26kg

2.00 g/kg

5.59

010f

3.05kg

2.95kg

2.98kg

 

2.00 g/kg

6.56

WAD = weight after death

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The dermal LD50 is greater than 2000 mg/kg. Since one death is observed at 2000 mg/kg this warrants classification in category 5 according to GHS criteria (table 3.1.1 note g-ii).
Executive summary:

Results:

Dose level

g/kg

No. Rabbits Dosed

No. of Death on Study Day

Cumulative Mortality

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

2.0

10

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

1/10

Percent mortality = 10%

95% Confidence Interval = 0-40%

The above data indicate that the dermal LD50 is greater than 2.0 g/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Multiple K1 studies from other peroxyesters.

Additional information

Justification for selection of acute toxicity – oral endpoint
K1: The study was performed according to OECD guidelines and GLP. LD50 >5000 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. As WoE the data for the analogues closest to the registered substance are included as WoE in the dossier. These are CAS 22288 -43 -3, CAS 424 -980 -8, and 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. 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.