myo-inositol-hexakisphosphate 3-phosphohydrolase

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3 December 1999 - 17 December 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

12 May 1981

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

31 July 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

dd. 23 December 1999

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

liquid

Details on test material:

Physical appearance: brown liquid
Storage conditions:in a freezer in the dark or, after thawing, in a refrigerator in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: not indicated
- Age at study initiation: 5-6 weeks
- Mean weight at study initiation: 324 g (males), 192 g (females)
- Fasting period before study:
- Housing: grouphousing (based on sex) in stainless steel cages fitted with wire-mesh floor and front
- Diet: Rat & Mouse No. 3 Breeding Diet RM3 (SDS Special Diets Services, Witham, England.
- Water: tap water suited for human consumption
- Acclimation period: 42-44 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.0-21.5
- Humidity (%): 40-62
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 3 December 1999 - 17 December 1999

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: the test material was diluted with water to diminish clogging of the nebulizer

Mass median aerodynamic diameter (MMAD):

3.2 µm

Geometric standard deviation (GSD):

1.3

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only inhalation chamber consisting of a cylindrical aluminium column, surrounded by a transparent cylinder.
- Exposure chamber volume: 50 L
- Method of holding animals in test chamber: Animals were secured in plastic animal holders (Batelle)
- Source and rate of air: 24.4 L/min
- System of generating particulates/aerosols: The test item was nebulized into smal droplets by using a compressed air driven nebulizer (Schlick, Coburg, Germany, type 970/S) at a constant pressure of 1.0 bar. The test item (130 g) was diluted with demineralized water (65 g) to diminish clogging of the nebulizer.
- Method of particle size determination: By gravimetric analysis (once per hour)
- Temperature, humidity, oxygen content, pressure in air chamber: 20.8 ± 0.21°C, 71 ± 2%, 21.1%, respectively
- Other: By securing a positive pressure in the central column and a slightly negative pressure in the outer cylinder, dilution of test atmosphere at the nose of the animals is prevented.

TEST ATMOSPHERE
- Samples taken from breathing zone: No, samples were taken by passing 10 L test atmosphere samples at 5 L/min through glass fibre filters.
- Brief description of analytical method used: An 11-stage cascade impactor (Institue's design) with the largest cut-off size of 4.2 µm was used.
- Particle size distribution and MMAD: see table 1

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: the starting concentration of 5 g/m^3 was selected based on international guidelines. Since no mortality occurred, no further groups were exposed.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5 g/m^3

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Visual observations for abnormal behaviour, clinical signs and mortality were performed just before exposure, during the treatment, at least once during the observation period and shortly after exposure. Bodyweights were recorded prior to exposure (day 0), on day 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

No statistics performed

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 150 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred.

Clinical signs:

other: A slightly decreased breathing rate was observed in two females at the second observation time, in all females at the third observation time and in all animals (male and female) at the last observation time. In addition, slight laboured breathing was obse

Body weight:

Mean overall bodyweight gain during the 14-day observation period was within the normal range expected for animals of this strain and age.

Gross pathology:

No abnormal macroscopic findings were found in any of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an acute inhalation study in male and female Wistar rats, performed according to OECD guideline 403 and GLP principles, the 4-hour LC50 of NPH 54 was >5.15 g/m^3.