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Toxicological information

Eye irritation

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Endpoint:
eye irritation: in vivo
Remarks:
in vivo study that was performed prior to current requirement for in vitro alternative testing
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 January 1982 - 16 April 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 January 1982 - 16 April 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Specific details on test material used for the study:
TEST MATERIAL
- name as cited in test report: p-diisopropylbenzene
- Molecular weight: 162 g/mol
- Molecular formula: C12H18
- Physical state: liquid
- Boiling point: 208°C at 760 mmHg

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability with H+; OH-; Heat, Light, H2: given
Species:
rat
Strain:
not specified
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
100 % as received
Doses:
3200 mg/kg
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 200 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed.
Clinical signs:
other:
Gross pathology:
No necropsies were conducted

The acute oral LD50 of this compound was greater than 3200 mg/kg in male and female rats. Clinical signs of toxicity included slight to moderat weakness and rough coats.

Interpretation of results:
other: EU GHS criteria not met
Conclusions:
Based on the results of this study, the acute oral LD50 for test item was greater than 3200 mg/kg in male and female rats. Clinical signs of toxicity included slight to moderate weakness and rough coats. 
Executive summary:

An acute oral toxicity study was conducted on rats. Based on the results of this study, the acute oral LD50 for test item was greater than 3200 mg/kg in male and female rats. Clinical signs of toxicity included slight to moderate weakness and rough coats. 

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 January 1982 - 16 April 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test was conducted according to an internal method.
GLP compliance:
not specified
Specific details on test material used for the study:
TEST MATERIAL
- name as cited in test report: p-diisopropylbenzene
- Molecular weight: 162 g/mol
- Molecular formula: C12H18
- Physical state: liquid
- Boiling point: 208 °C at 760 mmHg

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability with H+; OH-; Heat, Light, H2: given
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
occluded, single exposure, 24 hours
(guinea pig abdomen)
Duration of exposure:
24 hours
Doses:
single dose (dose up to 20 mL/kg)
Control animals:
no
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 20 mL/kg bw
Based on:
test mat.
Remarks on result:
other: = ca. 20000 mg/kg bw/d
Clinical signs:
other: erythema, edema, necrosis, eschars, scarring, desquamation and aloepcia

It produced moderate to severe erythema and edema and some necrosis initially; eschars were present after one week, and scarring, desquamation and alopecia were present after two weeks at doses ranging from 20 mL/g down to 1 mL/kg.


The dermal LD50 was greater than 20 mL/kg. 

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the results of this test, the acute dermal LD50 of test item was determined to be greater than 20 mL/kg bw (= ca. 20000 mg/kg bw/d).
Executive summary:

The acute toxicity to guinea pig in dermal test was performed. At most, test item is only slightly toxic by the dermal route. There was no evidence of percutaneous absorption. LD50 value was determined to be greater than 20mL/kg bw (= ca. 20000 mg/kg bw/d).

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Remarks:
in vivo study that was performed prior to current requirement for in vitro alternative testing
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 January 1982 - 16 April 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test was conducted according to an internal method.
GLP compliance:
no
Specific details on test material used for the study:
TEST MATERIAL
- name as cited in test report: p-diisopropylbenzene
- Molecular weight: 162 g/mol
- Molecular formula: C12H18
- Physical state: liquid
- Boiling point: 208 °C at 760 mmHg

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability with H+; OH-; Heat, Light, H2: given
Species:
guinea pig
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
other: depilated
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
single dose
Duration of treatment / exposure:
24 hours
Observation period:
2 weeks
Details on study design:
occluded, single exposure, 24 hours
(guinea pig abdomen)

and

open, Repeated (10 doses) - 5 animals
Irritation parameter:
overall irritation score
Basis:
animal:
Remarks on result:
other: Moderate erythema, edema and some necrosis.
Irritation parameter:
edema score
Basis:
animal:
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal:
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
The compound was a moderate skin irritant when applied to the depilated guinea pig abdomen under an occlusive wrap for 24 hours. It produced moderate erythema, edema and some necrosis. Thin eschars at one week, light scarring desquamation and alopecia at 2 weeks.

Occluded, single dose:


The compound produced moderate to severe erythema and edema and some necrosis initially; eschars were present after one week, and scarring, desquamation and alopecia were present after two weeks at doses ranging from 20 mL/g down to 1 mL/kg.


 


Open, Reapead (10 Doses) - 5 animals:


Moderate to severe erythema and edema replaced by thick, broken eschars at day 10.


Skin Absorption possible


 


Repeated daily application (10) of 0.5 mL of the material moderately exacerbated the initial response. Moderate to severe erythema and edema and petechial hemorrhages were present at day 1. By day 10, the application site in all animals was characterized by thick, broken eschars. Absorption of the compound through the skin was possible, since three of five animals in the repeated skin application test lost weight over the course of the study. 

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
p-diisopropylbenzene was rated a moderate irritant under the conditions of this study.
Executive summary:

p-diisopropylbenzene was a moderate skin irritant when applied to the depilated guinea pig abdomen under an occlusive wrap for 24 hours.


It produced moderate erythema, edema and some necrosis. Thin eschars at one week, light scarring desquamation and alopecia at 2 weeks.

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
in vivo study that was performed prior to current requirement for in vitro alternative testing
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 January 1982 - 16 April 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
only 10 animals tested, not many details provided in the report
Principles of method if other than guideline:
only 10 animals tested, not many details provided in the report
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
in vivo study that was performed prior to current requirement for in vitro alternative testing
Specific details on test material used for the study:
TEST MATERIAL
- name as cited in test report: p-diisopropylbenzene
- Molecular weight: 162 g/mol
- Molecular formula: C12H18
- Physical state: liquid
- Boiling point: 208 °C at 760 mmHg

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability with H+; OH-; Heat, Light, H2: given
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % as received
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 % as received
Day(s)/duration:
not specified
No. of animals per dose:
10
Details on study design:
no details given
Positive control substance(s):
no
Reading:
other: not specified
Group:
positive control
Dose level:
not specified
Remarks on result:
other: not specified
Reading:
other: not specified
Group:
negative control
Dose level:
not specified
No. with + reactions:
0
Remarks on result:
other: not specified
Reading:
other: not specified
Group:
test chemical
Dose level:
not specified
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: not specified

The material did not elicit a positive response when administreed to ten guinea pigs in a standardized skin sensitization test. 

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the results of this study, test item is not a dermal sensitizer in guinea pigs
Executive summary:

A skin sensitisation test was performed on guinea pigs. The material did no elicit a positive response when administered to ten guinea pigs in a standardized skin sensitization test.


Consequently, estimated human risk is low and the test substance was determined to be non-sensitizing in guinea pigs.

Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
26 January 1982 - 16 April 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
no
Limit test:
no
Specific details on test material used for the study:
TEST MATERIAL
- name as cited in test report: p-diisopropylbenzene
- Molecular weight: 162 g/mol
- Molecular formula: C12H18
- Physical state: liquid
- Boiling point: 198 °C at 760 mmHg

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability with H+; OH-; Heat, Light, H2: given
Species:
rat
Strain:
not specified
Sex:
male
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Rats were given a total of 11 treatments over a 15-day span
Frequency of treatment:
once daily
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Groups of five male rats were gavaged with 1000 or 100 mg compound/kg/day for a total of eleven treatments over a 15 day span.
A control group of five animals were gavaged with distilled water at a dose of 1000 mg/kg/day. Weight gain and feed intake were comparable between groups.
Control animals:
yes, concurrent vehicle
Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
No abnormal clinical signs were observed with the exception of a single high-dose animal exhibited porphyrin nasal discharge, weight loss and possible aspiration pneumonia.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Weight gain and feed intake were comparable between groups.
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
several slight but statistically-significant differences were noted in the high-dose group, including increased platelets and monocytes. All other indices (red blood cell count, hemoglobin concentration, hematocrit, red cell indices, white blood cell counts and the remaining portions of the differential white blood cell count) were comparable to controls.
No alterations in hematology were noted in blood from the low dose group.
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
A moderate decrease in serum glucose and a slight increase in creatinine in the high-dose animals; all other serum chemistry indices (alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, alkaline phosphatase, and urea nitrogen) were comparable to controls.
No alterations in serum clinical chemistry were noted in blood from the low dose group.
Endocrine findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
No significant changes in absolute or relative kidney or spleen weights were noted.
There was a trend which implied a dose dependent increase in relative liver weights were observed in the high-dose group.
Gross pathological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Enlarged hearts were observed in 3 of 5 rats in the high-dose group, which was considered to have occurred as a result of general respiratory stress associated with extensive consolidation of the lung (hypertrophy or the hearts might have been triggered by the consolidation in the lung).
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
Even though the enlarged hearts had been observed in the gross pathological examination, no compound related effects were seen at histopathological examination.
Histopathological findings: neoplastic:
not specified
Other effects:
not examined
Details on results:
The liver may be a site of toxic action, and the no effect level (NOEL) may be in the range of 100 mg/kg.
Key result
Dose descriptor:
NOEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Critical effects observed:
no
Conclusions:
A daily dose of 100 mg/kg was considered to be a no effect level (NOEL).
Executive summary:

The repeated dose toxicity test was done similar to OECD guideline 407. The test item was evaluated in a 2-week (subacute) oral toxicity study. Groups of five male rats were gavaged with 1000 or 100 mg compound/ kg/day for a total of eleven treatments over a 15 day span. A control group of five animals were gavaged with distilled water at a dose of 1000 mg/kg/day. The no effect level (NOEL) may be in the range of 100 mg/kg.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The eye irritation test was performed onto both eyes of 3 rabbits; in one eye of each rabbit, the material was immediately rinsed with water, while in the other eye, the material remained without washing.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
1,4-diisopropylbenzene
EC Number:
202-826-9
EC Name:
1,4-diisopropylbenzene
Cas Number:
100-18-5
Molecular formula:
C12H18
IUPAC Name:
1,4-bis(propan-2-yl)benzene
Specific details on test material used for the study:
TEST MATERIAL
- name as cited in test report: p-diisopropylbenzene
- Molecular weight: 162 g/mol
- Molecular formula: C12H18
- Physical state: liquid
- Boiling point: 208 °C at 760 mmHg

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: not specified
- Stability with H+; OH-; Heat, Light, H2: given

Test animals / tissue source

Species:
rabbit
Strain:
not specified

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Number of animals or in vitro replicates:
3animals
3 eyes washed, 3 eyes unwashed

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
animal: 1, 2, 3
Time point:
other: 1h
Remarks on result:
other: 3 of 3 animals with washing after treatment and 3 of 3 animals without washing after treatment showed slight irritation, limited to erythema of adnexa, resolved after one hour
Irritation parameter:
cornea opacity score
Basis:
animal: 1, 2, 3
Time point:
24/48/72 h
Score:
0
Reversibility:
other: not applicable
Remarks on result:
other: None of the three animals with washing after treatment and none of the three animals without washing after treatment showed Fluorescein stain on the cornea.
Irritation parameter:
conjunctivae score
Basis:
animal: 1, 2, 3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible
Remarks on result:
other: None of the three animals with washing after treatment and none of the three animals without washing after treatment showed Fluorescein stain on the adnexa. 1 hour after treatment the adnexa showed a slight erythema.
Irritation parameter:
iris score
Basis:
animal:
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritation parameter:
chemosis score
Basis:
animal:
Time point:
24/48/72 h
Score:
0
Remarks on result:
not measured/tested
Irritant / corrosive response data:
Irritation, limited to erythema of the adnexa, resolved after one hour. No adnexal or corneal staining was observed. Immediate washing was beneficial.

Any other information on results incl. tables

A very minor eye irritant.


 


The compound was a slight eye irritant when tested in six rabbit eyes (three washed and three unwashed). Irritation, limited to erythema of the adnexa, resolved after one hour. No adnexal or corneal staining was observed. Immediate washing was beneficial. 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the findings of this study, test item is slightly irritating to the eyes of rabbits. However, the criteria for classification and labelling according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008 are not met.
Executive summary:

The eye irritation test was performed onto both eyes of 3 rabbits; in one eye of each rabbit, the material was immediately rinsed with water, while in the other eye, the material remained without washing. Immediately after instillation, slight erythema was observed that was limited to the adnexa, and washing was palliative. No adnexal or corneal staining was observed.


Based on the results observed in the present study, the criteria for classification and labelling according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008 are not met.