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Administrative data

Description of key information

Acute toxicity:
- oral: LD50 > 5000 mg/kg bw
- dermal: LD50 > 2000 mg/kg bw
- inhalative: LC50 > 5 mg/L air (4 h exposure)

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:
From 23 May 1979 to 6 Jun 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
weight variation is higher than 20% of mean
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Sherman Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 - 300 g
- Fasting period before study: 24 h
- Diet: ad libitum
- Water: ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5 g/kg bw
Doses:
5000 mg/kg bw
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: weighing prior to and at the end of study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
No unusual behavioral signs were noted.
Body weight:
Prior to study: mean 220 g (males), 215 g (females)
End of study: mean 255 g (males), 235 g (females)
Gross pathology:
Gross pathological examination revealed nothing remarkable.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
Comparable to current guideline requirements and scientifically valid with acceptable restrictions.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
exposure time was only 1 hour
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: albino rats
Sex:
male/female
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: all glass exposure chamber
- Exposure chamber volume: 70 L
- System of generating particulates/aerosols: The air was passed through a desiccant prior to being passed through the test material.
- Rate of air: 10.0 L/min
- Temperature in air chamber: 70°F

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 3 - 5 µm
Analytical verification of test atmosphere concentrations:
no
Remarks:
concentration was calculated by differential weighing
Duration of exposure:
1 h
Concentrations:
20.5 mg/L (nominal)
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: weighing prior to and at the end of study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 20.5 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: calculated according to GHS
Mortality:
No mortality
Clinical signs:
other: Immediately after exposure the animals were wet, ruffled, agitated and raspy sounding. After 24 hours they appeared normal.
Body weight:
Prior to study: mean 205 g (males), 200 g (females)
End of study: mean 250 g (males), 235 g (females)
Gross pathology:
Gross pathologic examination revealed nothing remarkable.

According to GHS the value for dust (aerosol) has to be divided by 4 in order to compare 1 hour exposure to a 4 h exposure as recommended in the guideline. Thus, the value would be above 5 mg/L.

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
5 000 mg/m³
Quality of whole database:
The study was considerd as reliable for the assessment of the LC50.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
weight variation is higher than 20% of mean
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
other: albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: between 2.0 and 3.0 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back of animal
- Preparation: All animals had their backs clipped free 24 h prior to testing. All of the animals had their backs abraded prior to dosing.
- Type of wrap if used: large gauze patches and an impervious wrap around the trunk


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 100%
- Constant volume or concentration used: no, corrected for body weight
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
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: prior to and at the end of study
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
There were no unusual behavioral signs noted.
Body weight:
Prior to study: mean 2.44 kg (males), 2.23 kg (females)
End of study: mean 2.75 kg (males), 2.45 kg (females)
Gross pathology:
Gross pathologic examination revealed nothing remarkable.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Comparable to current guideline requirements and scientifically valid.

Additional information

Oral

Acute oral toxicity was tested in a study, where five male and five female albino Sherman-Wistar rats received an oral application of 5000 mg/kg bw of a test substance containing 91.3% di-(2-propylheptyl) phthalate and 8.7% 2-propylheptyl/4-methyl-2-propylhexyl/di-(4-methyl-2-propylhexyl)phthalate (Biosearch Inc., 1982). Prior to dosing, the rats were fasted for 24 hours and body weights were measured. After dosing, food and water were available ad libitum and daily observations were recorded for 14 days. Because no deaths and no unusual behavioral signs were observed, the LD50 for acute oral toxicity was estimated as > 5000 mg/kg bw.

 

Dermal

To analyze acute dermal toxicity, 2000 mg/kg of a test substance containing 91.3% di-(2-propylheptyl) phthalate and 8.7% 2-propylheptyl/4-methyl-2-propylhexyl/di-(4-methyl-2-propylhexyl)phthalate was applied to the backs of three male and three female albino rabbits (Biosearch Inc., 1982). The skin sites were previously clipped free of hair and then covered with gauze after application. 24 hours later, the dressings and excess materials were removed and for a period of 14 days, observations and mortalities were noted. Since no mortality and no unusual behavior signs were noted, the LD50 for acute dermal toxicity was determined to be > 2000 mg/kg.

 

By inhalation

The acute inhalation toxicity of DPHP was investigated in a group of 5 male and 5 female albino rats, which were exposed via whole-body inhalation to 20.5 mg/l di-(2-propylheptyl) phthalate aerosol (3-5 microns) of 91.3% purity [8.7% 2-propylheptyl/4-methyl-2-propylhexyl/di-(4-methyl-2-propylexyl) phthalate] for a period of one hour (Biosearch Inc., 1982). Thereby, the exposure was conducted in a 70 L all glass exposure chamber with an air flow rate of 10.0 l/min and a temperature of approximately 21 °C. During the 14 days observation period, no animals died and all gained body weight, although some clinical signs including wet and ruffled fur, agitation, and raspy sounds were noted. However, after 24 hours, the rats appeared normal. Since no mortality occurred and no abnormalities was found after pathological examinations, the LC50 was determined to be >20.5 mg/L after 1 h exposure. Following Haber’s Law, the value for the LC50 after 4 h exposure could be calculated as >5 mg/L air.

Justification for classification or non-classification

Due to the effect levels obtained in the acute toxicity studies, no classification according to GHS criteria is required.

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