2,4,8,10-tetra(tert-butyl)-6-hydroxy-12H-dibenzo[d,g][1,3,2]dioxaphosphocin 6-oxide, sodium salt

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(1981) Method B2, Commission Directive 92/69/EEC

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

85209-93-4

Cas Number:

85209-93-4

IUPAC Name:

85209-93-4

Constituent 2

Reference substance name:

12H-Dibenzo[d,g][1,3,2]dioxaphosphocin, 2,4,8,10-tetrakis(1,1-dimethylethyl)-6-hydroxy-,6-oxide, lithium salt

IUPAC Name:

12H-Dibenzo[d,g][1,3,2]dioxaphosphocin, 2,4,8,10-tetrakis(1,1-dimethylethyl)-6-hydroxy-,6-oxide, lithium salt

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS: Sprague-Dawley Crl:CD® (SD) IGS BR
- Source:Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200g - 350g
- Fasting period before study: none
- Housing:in groups of five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items: wooden chew blocks
- Diet (e.g. ad libitum): ad libidtum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany)
- Exposure chamber volume: 30 l
- Method of holding animals in test chamber: tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber
- Source of air: Compressed air, passed through a water trap and respiratory quality filters
- Method of particle size determination: Marple Personal Cascade Impactor, (Westech IS Ltd, Beds., UK); six impactor stages (9.6, 6.6, 3.5, 1.8, 0.87
and 0.33 μm cut points
- Treatment of exhaust air: passed through a scrubber trap, connected with a filter

- Samples taken from breathing zone: yes

TEST ATMOSPHERE (see Any other information on materials and methods incl. tables, table 1)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric method

Duration of exposure:

4 h

Concentrations:

see Any other information on materials and methods incl. tables, table 1

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: hourly during exposure, at the end of exposure and 1h later. Once daily up to 14 days.
and weighing: prior to exposure on the day of treatment, days 7 and 14.
- Necropsy performed: yes (all animal, surviving, died, killed)
- Other examinations performed: clinical signs, body weight, macroscopic examination, esp. of the respiratory tract, behavioural observations

Statistics:

LC50’s estimated by Linear Interpolation (US EPA, 1989)

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

3.11 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

see Any other information on results incl. tables, table 2

Clinical signs:

other: Common abnormalities:increased respiratory rate, hunched posture, pilo-erection and wet fur. Frequent instances of decreased respiratory rate, laboured respiration, noisy respiration, ataxia and red/brown staining around the head. Occasional instances of

Body weight:

Normal bodyweight development for all surviving animals during the study with the following exeptions:
Group 1: 1 male and 1 female showed reduced bodyweight gain or slight bodyweight loss during Week 1 but recovered to show normal development during Week 2. A further female from Group 1 showed slight bodyweight loss during Week 2.
Group 2: 5 females exhibited a reduced bodyweight gain or slight bodyweight loss during Week 1 but recovered to show normal development during Week 2.

Gross pathology:

Macroscopic abnormalities detected amongst
- animals that survived until Day 14 at necropsy:
Lungs – enlarged, fluid filled, abnormally dark, pale patches, dark patches (in all animals of the low and mid dose groups);
- animals that died or were humanely killed during the course of the study at necropsy:
Lungs – haemorrhagic, fluid filled, abnormally dark, pale patches;
Liver – dark;
Kidneys – dark or pale;
Stomach – gaseous distension; Small Intestine – gaseous distension; Large Intestine – gaseous distension.

Any other information on results incl. tables

Table 2: Mortality data

Group Number	Mean Achieved Atmosphere Concentration (mg/L)		Deaths
		Male	Female	Total
1	1.00	0/5	0/5	0/10
2	1.96	2/5	0/5	2/10
3	5.03	5/5	5/5	10/10

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Acute Toxicity Inhalation Category 4, H332: [Regulation (EC) No 1272/2008]