Diethyl phthalate

Endpoint summary

Description of key information

Acute toxicity:
Oral - LD50 = > 5 mL/kg
Inhalatiin - LC50 = > 511 ppm
Dermal: LD50 = > 10 mL/kg

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:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data considered reliable as copy of report received from the US EPA. Studies performed in accordance with 40 CFR part 716 for a chemical substance listed in Section 716.120 and processed for commercial purposes.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

According to Hagan, EC (1959) Acute Toxicity; Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, pp 17-25. Comparison with
OECD Test 401 suggests that with the exception of the absence of a control group and analysis of the formulations procedures and study design were similar to those prescribed in this guideline

GLP compliance:

not specified

Remarks:

GLP was just being introduced in 1978

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm Belvidere New Jersey USA
- Age at study initiation: Not reported
- Weight at study initiation: 139-164 g
- Fasting period before study: overnight prior to dosing
- Housing: assumed to be 5 animals/sex/group
- Diet (e.g. ad libitum): Wayne Animal Feeds available ad libitum except for overnight fast prior to dosing
- Water (e.g. ad libitum): ad libitum with possible exception of overnight prior to administration of test item
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

IN-LIFE DATES: From: 16th March 1978To: 31st March 1978

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Test Item used as supplied

Doses:

0.5, 1.0, 2.0 and 5.0 mL/kg

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed for signs of pharmacologic activity and/or toxicitys 1, 3, 6 and 24 hours post dose and daily thereafter for a total of 14 days. Weighed on intitiation and termination of the study
- Necropsy of survivors performed: Yes

Statistics:

The LD50 was calculated, including the 95% confidence limits) where possible using the method of Litchfield and Wilcoxon (Litchfield JT and Wilcoxon F (1949) J Pharmacol. Exptl.Therap. pp96-99,

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

> 5 mL/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 and 95% limits not calculable

Mortality:

One male animal given 5 mL/kg was sacrificed due to moribund condition on Day 5. Only signs observed from 24 hours after reciving the test item until sacrifice were slight depression and 28 g weight loss. No gross abnormalities at necropsy reported.

Clinical signs:

other: No clinical signs were oberved with the exception of 1 male dosed at 5.0 mL/kg that appeared slightly depressed within 24 hours of dosing and continued to Day 5 when it was humanely killed from the study.

Gross pathology:

With the exception of one male (dosed at 0.5 mL/kg) that was found to have fibrous tissue encasing the heart and lungs at necropsy, no abnormalities were found at gross necropsy of animals surviving the 14 day observation period.

Other findings:

None reported

One male rat given 5 ml/kg was sacrificed on day 5 following mild depression and bodyweight loss. In the absence of similar effects in other animals given the same dose this death may not be due to the test item.

Dose Level              Sex              Dead/Dosed              %            

                                                       (ml/kg)              5M:5F              0/5:0/5                     0

                                                               0.5            5M:5F              0/5:0/5                     0

1.0             5M:5F              0/5:0/5                     0

2.0             5M:5F              0/5:0/5                     0

5.0             5M:5F              0/5:0/5                     10

Result       LD50: > 5.0 ml/kg

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 was found to be greater than 5.0 mL/kg.

Executive summary:

Acute toxicity following administration of a single oral dose has been investigated in the rat. The LD50 was found to be in excess of 5 mL/kg body weight. At a density of 1.1181 the administered dose of 5 mL/kg equates to 5591 mg/kg body weight.

                                                                 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 591 mg/kg bw

Quality of whole database:

Acute toxicity has been investigated in rats, mice and rabbits. All findings indicate the substance to exhibit low tow toxicity by the oral route

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:

other: see 'Remark'

Remarks:

Hazardous Substances Data Bank (HSDB®) is a toxicology data file on the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET®). It focuses on the toxicology of potentially hazardous chemicals. It is enhanced with information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. All data are referenced and derived from a core set of books, government documents, technical reports and selected primary journal literature. HSDB is peer-reviewed by the Scientific Review Panel (SRP), a committee of experts in the major subject areas within the data bank's scope. HSDB is organized into individual chemical records, and contains over 5000 such records. This study was performed before the introduction of OECD guidelines and GLP. Limited details available on methodology.

Principles of method if other than guideline:

To determine the effects, in rats, of acute inhalation exposure

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole body inhalation chamber
- Exposure chamber volume: No data
- Method of holding animals in test chamber: No data
- Source and rate of air: No data
- Method of conditioning air: No data
- System of generating particulates/aerosols: Air was bubbled through diethyl phthalate at 150 deg C
- Method of particle size determination: No data
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: No data

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

6 h

Concentrations:

511 ppm (4.64 mg/L)

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No data

Statistics:

Not applicable

Sex:

not specified

Dose descriptor:

LC50

Effect level:

>= 511 ppm

Exp. duration:

6 h

Sex:

not specified

Dose descriptor:

LC50

Effect level:

>= 4.64 mg/L air (nominal)

Exp. duration:

6 h

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions in which this study was conducted LD50 was >511 ppm when administered by the inhalation route for 6 hours.

Executive summary:

Under the conditions in which this study was conducted, no mortality occurred when rats were exposed to a saturated vapour of 511 ppm (4.64 mg/L) by the inhalation route for 6 hours.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

4 640 mg/m³ air

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:

16 - 31 March 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted in 1978 before the introduction of GLP and OECD methodology.

Qualifier:

according to guideline

Guideline:

other: Hagan EC (1959) Acute toxicity in Appraisal of the Safety of chemicals in foods, drugs and cosmetics, pp 17-25

Principles of method if other than guideline:

Four groups of 3male and 3 female albino rats were given doses of 1.0, 2.0, 5.0 and 10.0 ml/kg, applied to the shaved mildly abraded skin under an occlusive patch for 24 h then observed for 14 days. The DEP was used as received. Animals were observed for signs of pharmacologic activity and toxicity 1, 3, 6 and 24 hours post application and daily thereafter for a total of 14 days. Animals sacrificed at the end of the 14 day observation period were subjected to a complete gross necropsy.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey, USA
- Age at study initiation: Not reported
- Weight at study initiation: Males: 140 - 170g; females: 154 - 178g
- Fasting period before study: no
- Housing: standard laboratory conditions
- Diet (e.g. ad libitum): Wayne animal feed
- Water (e.g. ad libitum): yes
- Acclimation period: yes, period not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): standard laboratory conditions
- Humidity (%): standard laboratory conditions
- Air changes (per hr): standard laboratory conditions
- Photoperiod (hrs dark / hrs light): standard laboratory conditions

IN-LIFE DATES: From: 16 March To: 31 March 1978

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Not reported
- % coverage: 10
- Type of wrap if used: gauze patches covered by an impermeable plastic wrapping

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: immediately

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.0, 2.0, 5.0 or 10 ml/kg
- Concentration (if solution): 100% as supplied
- Constant volume or concentration used: no
- For solids, paste formed: yes/no

VEHICLE
- Amount(s) applied (volume or weight with unit): N/A
- Concentration (if solution): N/A
- Lot/batch no. (if required): N/A
- Purity: N/A

Duration of exposure:

24 hours

Doses:

1.0, 2.0, 5.0 or 10 mL/kg

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs - 1, 3, 6 and 24 hours following dosing and daily thereafter for a total of 14 days. Body weight recorded at initiation and termination.
- Necropsy of survivors performed: yes

Statistics:

Not required as there were no deaths and an LD 50 could not be calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 mL/kg bw

Based on:

test mat.

Mortality:

None in any dose group.

Clinical signs:

other: Skin slightly reddened in all animals when dressings removed

Gross pathology:

No abnormalitities detected

Other findings:

None reported

LD50 > 10 ml/kg

Dose Level              Sex              Dead/dosed              % Mortality

(ml/kg)                      M:F

1.0                            3:3                    0/3:0/3                     0:0

2.0                            3:3                     0/3:0/3                     0:0

5.0                            3:3                     0/3:0/3                     0:0

10.0                         3:3                      0/3:0/3                     0:0

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 > 10 ml/kg

Executive summary:

Acute toxicity following administration of a single dermal dose over a 24 hour period has been investigated in the rat. The LD50 was determined to be in excess of 10 mL/kg body weight. This equates to a dose level of 11181 mg/kg when corrected for density.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

11 181 mg/kg bw

Additional information

Acute toxicity following administration of a single oral dose has been investigated in the rat. The LD50 was found to be in excess of 5 mL/kg body weight (5591 mg/kg when corrected for density).

A poorly documented study by the inhalation route indicates no mortality to have occurred when rats were exposed to a saturated vapour of 511 ppm (4.64 mg/L) by the inhalation route for 6 hours.

Acute toxicity following administration of a single dermal dose over a 24 hour period has been investigated in the rat. The LD50 was determined to be in excess of 10 mL/kg body weight (11181 mg/kg when corrected for density).

Justification for selection of acute toxicity – oral endpoint
Best documented of the studies available

Justification for selection of acute toxicity – inhalation endpoint
Single study available

Justification for selection of acute toxicity – dermal endpoint
Single study available

Justification for classification or non-classification

Acute toxicity has been investigated by the oral and dermal and inhalation routes of exposure. The outcome of these studies does not indicate a justification for classification according to the criteria of Regulation (EC) No. 1272/2008.