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Description of key information

Acute oral toxicity: The acute oral toxicity of the test item was examined in a study equivalent to OECD guideline 401. The LD50 value was determined to be 1575.3 mg/kg bw.
Acute inhalation study: The acute inhalation toxicity of the test item was determined in a study equivalent to OECD guideline 403. The LC50 value was determined to be 1.5 mg/L. 
Acute dermal toxicity: The acute dermal toxicity of the test item was determined according to OECD guideline 402. The LD50 was determined to be >2000 mg/kg bw.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: From the Institute´s colony
- Age at study initiation: Young adult
- Weight at study initiation: Males: 196 to 298 g, females: 87 to 150 g
- Fasting period before study: Before dosing the rats fasted overnight
- Housing: Housed in groups of five in screen-bottomed stainless steel cages, in a well-ventilated room

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 1°C
Route of administration:
oral: gavage
Vehicle:
other: shellsol T
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 %

MAXIMUM DOSE VOLUME APPLIED: 6.22 mL/kg bw

Doses:
3.00, 3.60, 4.32, 5.18 or 6.22 mL/kg bw equivalent to 2670, 3204, 3844.8, 4610.2, 5535.8 mg/kg bw
No. of animals per sex per dose:
groups of 5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, macroscopic examinations
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 575.3 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 424 - <= 1 735.5
Remarks on result:
other: Conversion of mg/kg bw based on density of 0.89
Mortality:
2670 mg/kg bw: 3/10
3204 mg/kg bw: 4/10
3844.8 mg/kg bw: 9/10
4610.2 mg/kg bw: 9/10
5535.8 mg/kg bw: 10/10
Clinical signs:
Within a few hours after dosing the rats showed sluggishness, sedation and ataxia. Later on coma was frequently observed.
Body weight:
not examined
Gross pathology:
Macroscopic examination of the survivors did not reveal any treatment-related gross alterations.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral toxicity of the test item was examined in a study equivalent to OECD guideline 401. The LD50 value was determined to be 1575.3 mg/kg bw.
Executive summary:

The acute oral toxicity of the test item was examined in a study equivalent to OECD guideline 401. The test substance was applied in doses of 3.00, 3.60, 4.32, 5.18 or 6.22 mL/kg bw equivalent to 2670, 3204, 3844.8, 4610.2, 5535.8 mg/kg bw. The test material was given by gavage as 50 % dilution in shellsol T to groups of 5 male and 5 female albino rats. The LD50 value was determined to be 1575.3 mg/kg bw. Mortality occured between 2 hours and 3 days after treatment. Animals died from 3 mL/kg bw onwards. The rats showed sluggishness, sedation and ataxia. Later on come was frequently observed. The survivors recovered gradually and looked quite healthy again at the end of the observation period.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 575.3 mg/kg bw
Quality of whole database:
Study is equivalent to OECD guideline, no GLP study.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979-05-09 to 1979-06-14
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 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
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: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands
- Weight at study initiation: males: 180 g, females: 135 g
- Fasting period before study: none
- Housing: 5 animals per cage, stainless steel cages
- Diet: ad libitum the Institute's stock diet for rats
- Water: ad libitum unfluoridated water

ENVIRONMENTAL CONDITIONS
- Temperature: 21 +/- 1 °C
- Humidity (%): 50-60


Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel exposure chamber
- Exposure chamber volume: 1.5 m3
- Source and rate of air: total airflow of 1.6 m3/h
- System of generating particulates/aerosols: nebulizer provided with a baffle to remove large rdroplets from the mist produced
- Method of particle size determination: particle size determinations and counts were carried out in samples taken from the atmosphere in the chamber with a Cascade Impactor

TEST ATMOSPHERE
- Brief description of analytical method used: analysis of the test atmosphere was performed gravimetrically, samples were takne by passing a measured quantity of the test atmosphere through a Cambridge glassfibre filter at intervals of about 1.5 h
- Samples taken from breathing zone: yes
- Particle size distribution: maximum diameter 6.7 µm, 80 % of the mist consisted of droplets with a diameter of 1.7-3.3 µm


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2.56, 1.77, 1.55, 1.38, 1.30 g/m3 (measured)
No. of animals per sex per dose:
5
Control animals:
no
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 500 mg/m³ air
Based on:
test mat.
95% CL:
1 400 - 1 610
Exp. duration:
4 h
Mortality:
All animals of the highest dose group died until day 4 as well as 2 males and all females of the 1.77 g/m3 dose group, 3 males and 4 females of the 1.55 g/m3 dose group, 2 males and 2 females of the 1.38 g/m3 dose group and 2 males of the lowest (1.3 g/m3) dose group.
Clinical signs:
other: Restlessness during the first half an hour was observed. During exposure, animals kept their eyes closed and some had wet noses. After exposure mouth breathing was observed in the higher doses.
Body weight:
Animals lost weight during the first week of observation period. Surviving animals gained weight during the second week.
Gross pathology:
no data
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the LC 50 value of 1.5 g/m3 (1.5 mg/L) the test substance has to be classified for acute toxicity after inhalation into category 4.
Executive summary:

The acute inhalation toxicity of the test substance (60 % in Di-isobutyl phthalate) was tested on 50 male and 50 female Wistar rats. The animals were individually exposed to the aerosol at concentrations of 2.56, 1.77, 1.55, 1.38 and 1.30 g/m3 (5 males anf 5 females per doese group) for 4 hours. The animals were observed for a period of 14 days afterwards. All animals of the highest dose group died until day 4 as well as 2 males and all females of the 1.77 g/m3 dose group, 3 males and 4 females of the 1.55 g/m3 dose group, 2 males and 2 females of the 1.38 g/m3 dose group and 2 males of the lowest (1.3 g/m3) dose group. Restlessness during the first half an hour of exposure was observed. During exposure, animals kept their eyes closed and some had wet noses. After exposure mouth breathing was observed in the higher doses. A weight loss was observed during the first week of the observation period, but the surviving animals gained weight again in the second week. An LC 50 value of 1.5 mg/L was detemined.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 500 mg/m³
Quality of whole database:
Study is equivalent to OECD guideline, no GLP study.

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:
1994-07-13 to 1995-01-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
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: Iffa Crédo, 69210 L'Arbresle, France
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: Male: 257 +/- 13 g, Female: 218 +/- 10 g
- Housing: The animals were housed in polycarbonate cages covered with a stainless steel lid.
- Diet: A04 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France)
- Water: Drinking water filtered by a F.G. Millipore membrane (0.22 micron) was contained in bottles
- Acclimation period: At least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Area of skin representing 5 x 6 cm for the females and 5 x 7 cm for the males of the body surface of the animals.
- % coverage: 10 %
- Type of wrap if used: A hydrophilic gauze pad (Semes France, 54183 Heillecourt, France)

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
Evaluation of the innoxiousness or toxicity of the test substance following a single dermal application in rats should include the relationship, if any, between the animals' exposure to the test substance and the incidence and severity of all the abnormalities including behavioural and clinical abnormalities, macroscopic lesions, body weight changes, mortality and any other toxic effects.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the observation period.
Clinical signs:
No clinical signs were observed during the study.
In all males, moderate erythema (grade 2) and slight or moderate oedema (grade 2 or 3) were observed from day 2 to day 4. No sign of erythema or oedema was noted after day 4. Dryness of the skin was observed at the test site from day 3 to day 10. All cutaneous reactions had subsided on day 13.
In females, moderate erythema (grade 2) and slight or moderate oedema (grade 2 or 3) were seen the day after treatment. Oedema (grade 2) persisted in 2 animals only the next day. Moderate to marked erythema persisted in all animals up to day 6. Crusts were noted in 2 females on days 3 and 4 and in all animals on days 5 to 9. Dryness of the skin was observed at the test site on day 5 to day 9 or 12. All cutaneous reactions had subsided on day 13.
Body weight:
Slight decrease in body weight gain was noted in both sexes the first week. The second week, body weight gain was comparable to historical control data from animals of the same age, strain supplier, sex and initial body weight.
Gross pathology:
Macroscopic examination of the main organs of the animals killed at the end of the study revealed no apparent abnormalities.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal toxicity of the test item was determined according to OECD guideline 402. The LD50 was determined to be >2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test item was determined according to OECD guideline 402. The test substance (50 % purity) was applied semi-occlusively to the skin of rats at a dose of 2000 mg/kg bw. 5 males and 5 females showed no mortality after an exposure period of 24 hours and an observation period of 14 days. The LD50 was determined to be > 2000 mg/kg bw. The animals were also checked for clinical signs, body weight gain and necropsy. The general behaviour of the animals was not affected by treatment. Moderate to marked cutaneous reactions were observed in both sexes the first 4 -6 days after treatment. All signs of skin irritation had subsided by day 13.

Slight decreased body weight gain was observed in both sexes the first week only. No death occured at 2000 mg/kg bw. A macroscopic examination revealed no abnormalities in the animals killed at the end of the study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLPD and guideline study

Additional information

Acute oral toxicity

The acute oral toxicity of the test item was examined in a study equivalent to OECD guideline 401. The test substance was applied in doses of 3.00, 3.60, 4.32, 5.18 or 6.22 mL/kg bw equivalent to 2670, 3204, 3844.8, 4610.2, 5535.8 mg/kg bw. The test material was given by gavage as 50 % dilution in shellsol T to groups of 5 male and 5 female albino rats. The LD50 value was determined to be 1575.3 mg/kg bw. Mortality occured between 2 hours and 3 days after treatment. Animals died from 3 mL/kg bw onwards. The rats showed sluggishness, sedation and ataxia. Later on come was frequently observed. The survivors recovered gradually and looked quite healthy again at the end of the observation period.

Acute inhalation study

The acute inhalation toxicity of the test substance (60 % in Di-isobutyl phthalate) was tested on 50 male and 50 female Wistar rats. The animals were individually exposed to the aerosol at concentrations of 2.56, 1.77, 1.55, 1.38 and 1.30 g/m3 (5 males anf 5 females per doese group) for 4 hours. The animals were observed for a period of 14 days afterwards. All animals of the highest dose group died until day 4 as well as 2 males and all females of the 1.77 g/m3 dose group, 3 males and 4 females of the 1.55 g/m3 dose group, 2 males and 2 females of the 1.38 g/m3 dose group and 2 males of the lowest (1.3 g/m3) dose group. Restlessness during the first half an hour of exposure was observed. During exposure, animals kept their eyes closed and some had wet noses. After exposure mouth breathing was observed in the higher doses. A weight loss was observed during the first week of the observation period, but the surviving animals gained weight again in the second week. An LC 50 value of 1.5 mg/L was detemined.

Acute dermal toxicity

The acute dermal toxicity of the test item was determined according to OECD guideline 402. The test substance (50 %) was applied semi-occlusively to the skin of rats at a dose of 2000 mg/kg bw. 5 males and 5 females showed no mortality after an exposure period of 24 hours and an observation period of 14 days. The LD50 was determined to be > 2000 mg/kg bw. The animals were also checked for clinical signs, body weight gain and necropsy. The general behaviour of the animals was not affected by treatment. Moderate to marked cutaneous reactions were observed in both sexes the first 4 -6 days after treatment. All signs of skin irritation had subsided by day 13.

Slight decreased body weight gain was observed in both sexes the first week only. No death occured at 2000 mg/kg bw. A macroscopic examination revealed no abnormalities in the animals killed at the end of the study.

Justification for classification or non-classification

Self-Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the results the substance is considered to be classified as acute oral toxicity category 4., H302, and acute inhalation toxicity cat. 4, H332 under Regulation (EC) No 1272/2008.

The substance contains up to 40 % isododecane as stabilizer which is classified as aspiration toxicity cat. 1. Based on the kinematic viscosity of the substance and in accordance with the section 3.10.3 of Annex I of Regulation (EC) No 1272/2008 (CLP) the substance has to be classified as aspiration toxicity cat. 1, H304: May be fatal if swallowed and enters airways.