Phthalic acid

Endpoint summary

Description of key information

The acute oral toxicity of Phthalic Acid is low. LD50 values >2000 mg/kg were reported in mice and rats.

In an acute inhalation study in rats, the aerolized test substance proved to have essentially no acute inhalation toxicity. The LC50 was >5058 mg/m³ in male and female rats.

There are no data on acute dermal toxicity available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No OECD guideline or GLP defined. No doses defined.

Principles of method if other than guideline:

male and female albino mice weighing 18-20 g, were used. The animals were fasted for a period of 4-16 h prior to treatment. Range-finding tests of the acute toxicity were conducted initially. 5% gum acacia was used as the vehicle. All surviving animals were maintained for a subsequent 14-day period. The LD50 was calculated from the mortality data.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

Breeder: Canadian Breeding Laboratories and Charles River Laboratories
weight at study initiation: 18-20g
fasting period: 4 to 16 hours prior to treatment

Route of administration:

oral: unspecified

Vehicle:

other: 5% gum acacia

Details on oral exposure:

All surviving animals were maintained for a subsequent 14-day period. The LD50 was calculated from the mortality data according to Lichfield and Wilcoxan (1949).

Doses:

no data

No. of animals per sex per dose:

10

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Phthalic acid, Mouse,LD50= >5000 mg/kg bw

Executive summary:

In an acute oral toxicity study in male and female albino mice the LD50 was >5000 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: insufficient data documentation

Principles of method if other than guideline:

no data

GLP compliance:

not specified

Test type:

other: Acute oral toxicity in rats

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

no data

No. of animals per sex per dose:

no data

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 8 000 mg/kg bw

no data

Executive summary:

In an acute oral toxicity study the LD 50 in rats was 8000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

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:

2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

other: Acute inhalation toxicity study in rats

Limit test:

no

Species:

rat

Strain:

Wistar

Remarks:

Hsd Cpb:WU (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan-Nederland, AD Horst
- Age at study initiation: approximately 2 months
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 3°C
- Humidity (%): 40-60%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 2010

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Remark on MMAD/GSD:

The respirability of the aerosol was adequate, i.e. the mass median aerodynamic diameter (MMAD) was 3.1µm, the geometric standard deviation (GSD) was 1.9).
Test item was micronized.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

stability was certified for the duration of the study

Duration of exposure:

4 h

Concentrations:

5058 mg/m³

No. of animals per sex per dose:

3

Control animals:

yes

Details on study design:

The respirability of the aerosol was adequate, i.e. the mass median aerodynamic diameter (MMAD) was 3.1µm, the geometric standard deviation (GSD) was 1.9).
Body weights were measured before exposure, on days 1, 3, 7 and weekly thereafter. 2 week observation period.

Statistics:

yes

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 058 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Mortality did not occur up the maximum technically attainable concentration.

Clinical signs:

other: bradypnea, irregular breathing patterns, labored breathing patterns, nasal discharge (serous), nose: red encrustations, muzzle: red encrustations; motility reduced, limp, tremor, high-legged gait, lurching, piloerection, cyanosis, and hypothermia

Remarks:

non-specific effects, related to the high concentration of dry, highly respirable dust 'overloading' to some extent the upper airways of the respiratory tract

Body weight:

no changes in body weight of toxicological significance

Gross pathology:

The macroscopic findings were essentially indistinguishable amongst exposure and control group.

Other findings:

no changes in reflexes investigated on the first post-exposure day; rectal temperature significantly reduced in exposed animals

Summary of acute inhalation toxicity-4 hour exposure (aerosolization of the micronized test article powder):

No of animals, sex	Target concentration (mg/m³)	Toxicological Result	Onset and duration of Signs	Onset and Duration of Mortality	Rectal Temperature
5 m	0	0 / 0 / 5	-	-	37.9
3 m	5000	0 / 3 / 3	0d-1d	-	30.1**
5 f	0	0 / 0 / 5	-	-	38.4
3 f	5000	0 / 3 / 3	0d-2d*	-	33.3**

N- group assignment, m= males, f=females.

*- one female rat showed hairless areas (from day 1 -14) which is not considered to be substance-related and therefore is not concluded in the incidence tables.

**- p<0.01

´Toxicological results´ colum are: 1st= number of dead animals, 2nd= number of animals with signs after cessation of exposure; 3rd= number of animals exposed.

Executive summary:

A study on the acute inhalation toxicity of Phthalic acid on rats has been conducted in accordance with the EU Directive 92/69/EEC, and especially OECD GD 403 (2009). One group of rats was nose-only exposed to powder aerosol in concentrations of 5058 mg/m³. The powder aerosol was generated so that it was respirable to rats. Mortality did not occur up the maximum technically attainable concentration. Rats exposed at 5058 mg/m³ displayed the following signs (exposure day up to second post exposure day): bradypnea, irregular breathing patterns, labored breathing patterns, nasal discharge (serous), nose: red encrustations, muzzle: red encrustations; motility reduced, limp, tremor, high-legged gait, lurching, piloerection, cyanosis, and hypothermia. The respirability of the aerosol was adequate, i.e. the mass median aerodynamic diameter (MMAD) was 3.1µm, the geometric standard deviation (GSD) was 1.9).

The results can be summarized as follows:

LC50 inhalation (powder aerosol, 4h), male/female rat: >5058 mg/m³.

NOAEL male and female rat: <5058 mg/m³

The aerolized test substance proved to have essentially no acute inhalation toxicity in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 058 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a study conducted in male and female albino mice, an oral LD50 >5000 mg/kg bw was found (Schoneker, 2002).

In a second study in mice the LD50 was found to be 2530 mg/kg bw (Lin, 1982).

These values are supported by 2 studies in rats in which LD50 values were found to be 8000 and 7900 mg/kg respectively (Tomita, 1978; Giam, 1984), however the reliability of these studies can not be assessed due to limited documentation.

A study on the acute inhalation toxicity of Phthalic acid on rats has been conducted in accordance with the EU Directive 92/69/EEC, and especially OECD GD 403 (2009). One group of rats was nose-only exposed to powder aerosol in concentrations of 5058 mg/m³. The powder aerosol was generated so that it was respirable to rats. Mortality did not occur up the maximum technically attainable concentration. Rats exposed at 5058 mg/m³ displayed the following signs (exposure day up to second post exposure day): bradypnea, irregular breathing patterns, labored breathing patterns, nasal discharge (serous), nose: red encrustations, muzzle: red encrustations; motility reduced, limp, tremor, high-legged gait, lurching, piloerection, cyanosis, and hypothermia. The respirability of the aerosol was adequate, i.e. the mass median aerodynamic diameter (MMAD) was 3.1µm, the geometric standard deviation (GSD) was 1.9).

The results can be summarized as follows:

LC50 inhalation (powder aerosol, 4h), male/female rat: >5058 mg/m³.

NOAEL male and female rat: <5058 mg/m³

The aerolized test substance proved to have essentially no acute inhalation toxicity in rats (Pauluhn, 2009).

There are no data on acute dermal toxicity available.

Justification for classification or non-classification

Based on the available studies, the test substance needs no classification for acute toxicity according to EU Regulation.