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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes (incl. QA statement)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

286-344-4

EC Name:

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

Cas Number:

85209-91-2

Molecular formula:

C29H43O4P.Na

IUPAC Name:

sodium 5,7,13,15-tetra-tert-butyl-10-oxo-9,11-dioxa-10λ⁵-phosphatricyclo[10.4.0.0³,⁸]hexadeca-1(12),3,5,7,13,15-hexaen-10-olate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Sprague-Dawley origin (Hsd:Sprague-Dawley (CD))
- Source: Harlan U.K. Ltd., Bicester, Oxon, England.
- Age at study initiation: 8 - 11 weeks
- Weight at study initiation: 221 - 260 g
- Housing: individually in metal cages (RS Biotech Sub-Dividable Rodent Cages - polished stainless steel) until Day 4 when they were returned to group housing. Cages fitted with grid floors.
- Diet (e.g. ad libitum): standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet)
- Water (e.g. ad libitum): drinking water
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 40 - 70%
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: 48% aqueous methycellulose

Details on dermal exposure:

dorso-lumbar region
- Area of exposure: approximately 50 mm x 50 mm
- % coverage: 10
- Type of wrap if used: waterproof dressing (encircled firmly around the trunk of the animal)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with warm water (30-40°C), blotted dry with absorbent paper
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution):48% w/v
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 4,17 ml

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

10 rats (5 of each sex)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation of clinical signs after dosing, at frequent intervals of this day 1, day 2-14 twice daily,
day 15 in the morning, local dermal irritation daily observed
weighing day 1 (prior to dosing), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: local dermal irritation (erythema, eschar formation, oedema formation), any other lesion or reaction (spots, scabbing)

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: none

Gross pathology:

no abnormalities

Other findings:

dermal reactions: very slight dermal irritation (erythema and/or oedema), resolving completely on day 4. Scabbing and/or spots in 3 females on day 6, resolving completely by day 7, 9, 11.

Applicant's summary and conclusion

Interpretation of results:

other: LD50 > 2000 mg/kg

Conclusions:

No labelling regarding acute dermal toxicity according to Regulation (EC) No 1272/2008 is required.