Phthalic acid

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Phthalic acid

EC Number:

201-873-2

EC Name:

Phthalic acid

Cas Number:

88-99-3

Molecular formula:

C8H6O4

IUPAC Name:

benzene-1,2-dicarboxylic acid

Details on test material:

Phthalic Acid LP RJE 73330, Stability certified for the duration of study.

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.