Phosphoric acid, mixed esters with biphenyl-4,4'-diol and phenol

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

of 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

of 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sprague Dawley rats, strain: Crl:CD (SD) IGS BR with appropriate range of bodyweight at study start.
- Source: Charles River UK Ltd., Margate, Kent, UK.
- Age at study start (day of dosing): 8 to 12 weeks.
- Weight at start (day of dosing): Females: minimum 205 g, maximum 243 g.
- Housing: Group housing with up to 4 animals in suspended solid-floor propylene cages.
- Bedding material: Woodflakes.
- Fasting period: Overnight immediately prior to dosing until 3-4 hours post administration.
- Diet (ad libitum, except for fasting period): Commercially available standard laboratory animal diet:
Certified Rat and Mouse Diet
- Water (ad libitum*): Mains drinking water
- Acclimation period: At least 5 days before start of dosing.

* Remark: The study report does not clearly state whether or not water was supplied during the fasting period.

ENVIRONMENTAL CONDITIONS

The animal room was maintained at target ranges of:
- Temperature (°C): 22 ± 3°C
- Relative Humidity (%): 30 to 70%
- Photoperiod: 12 h day / 12 h night
- Rate of air exchange: At least 15 changes/h

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Target dose of test material --- Concentration of test material in vehicle: 300 mg/kg bw --- 30 mg/mL
2000 mg/kg bw --- 200 mg/mL
- Amount (dose volume by gavage): 10 mL/kg bw
(individual dose volume was calculated based on individual fasted bodyweight at the time of dosing).

DOSAGE PREPARATION:
The test material, was freshly prepared as a solution in dimethyl sulphoxide (DMSO). DMSO was used as a vehicle, because the test material did not dissolve in distilled water or arachis oil BP.

RATIONALE FOR DOSE SELECTED:
The choice of the limit dose of 2000 mg/kg bw was appropriate in the main test, because doses of 300 mg/kg and 2000 mg/kg did not induce any deaths, clinical signs of toxicity, adverse effects on bodyweight or necropsy findings in sequential preliminary sighting studies with 1 female rat/dose.

Doses:

300 mg/kg bw (1 female)
2000 mg/kg bw (5 females)

No. of animals per sex per dose:

5 (females only)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observation of clinical signs: 0.5, 1, 2 and 4 h post dosing on the day of administration (Day 0) and subsequently once daily for 14 days.
Weighing of each animal: Day 0 for dose calculation and on Days 7 and 14.
- Necropsy performed: yes, of all sighting and main study animals.

Statistics:

Not applicable, as there were no deaths

Preliminary study:

There were no deaths, clinical signs of toxicity, adverse effects on bodyweight or necropsy findings in a preliminary sighting study at a dose of 300 mg/kg bw administered to 1 female rat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths at 300 mg/kg (sighting) and at the limit dose of 2000 mg/kg

Mortality:

Single Dose at Mortality
300 mg/kg 0/1 (f)
2000 mg/kg 0/5 (f)

Clinical signs:

other: Clinical signs of systemic toxicity were not evident.

Gross pathology:

Necropsy of each animal at the end of the 14-day post treatment observation period did not reveal any macroscopic pathology findings.

Conclusions:

In view of the oral LD50 > 2000 mg/kg bodyweight attained in the present study, its outcome does not necessitate any classification or labelling regarding acute oral toxicity according to EU regulations (REGULATION (EC) 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 28 - February 11, 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

of 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

of 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

of 1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Wistar rats, strain: Crl:WI (Han) (outbred, SPF-Quality), with appropriate range of bodyweight at study start.
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation (day of dosing): Approx. 12 weeks.
- Weight at study initiation( day of dosing): Mean (males): 337 g, minimum 324 g, maximum 349 g.
Mean (females): 211 g, minimum 207 g, maximum 217 g.
- Housing: Individual housing in M III type cages. (During acclimatization group housing in M IV type cages).
- Bedding material: Sterilized sawdust (Litalabo, S.P.P.S., Argenteuil, France).
- Cage enrichment: Paper (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, UK).
- Diet (ad libitum): Commercially available rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (ad libitum): Tap water
- Acclimation period: At least 5 days before treatment start under laboratory conditions.

Routine analysis of the sawdust, paper, diet and water, did not provide evidence of contamination that might have affected the study integrity.


ENVIRONMENTAL CONDITIONS

Animal housing and environmental conditions were appropriate for acute toxicity testing in the rat: Controlled environment with approximately 15 airchanges per hour, 12 hours artificial fluorescent light and 12 hours darkness per day, 19.0 - 20.5°C and 48 – 78% relative humidity. Due to a technical failure of the temperature and relative humidity sensors in the animal room in which in which the animals were housed, the temperature and relative humidity records were taken from another animal room connected to the same temperature and relative humidity regulation system and therefore considered to be representative for the present study.

Type of coverage:

occlusive

Vehicle:

polyethylene glycol

Remarks:

400 (Merck, Darmstadt, Germany)

Details on dermal exposure:

TEST SITE
- Preparation: One day before exposure an area of approximately 5x7 cm on the back of the animal was clipped. During health inspection of the animals prior to commencement of treatment, special attention was paid to the skin to be treated, which was intact and fre e from any abnormality.
- Area of treated skin: Ca. 25 cm2 in males, ca.. 18 cm2 in females corresponding to ca. 10% of total body surface.
- Type of wrap used: Surgical gauze patch (Surgy 1 D), successively covered with aluminium foil and Coban elastic bandage. For females additional
fixation of the bandage with Micropore tape.

REMOVAL OF TEST SUBSTANCE
Occlusive treatment of the clipped, intact skin lasted 24 hours. Then the dressings (gauze, foil, bandages, tape) were removed and residual test substance washed off the skin with tap-water.

TEST MATERIAL AND DOSE PREPARATION
- Administered Dose of test substance: 2000 mg/kg bw
- Administration Volume: 10 mL per kg body weight (specific gravity of the vehicle of 1.125 was accounted for)

The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level.

- Justification for choice of vehicle:
Trial formulations at the testing laboratory and test substance data supplied by the sponsor led to the choice of this vehicle.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Duration of the observation period following administration start (day 1) was 14 days during which mortality/survival and clinical signs were recorded at: 0, 2 and 4 hours after administration start on day 1 and twice daily (mortality/survival) or once daily (clinical signs) thereafter until day 15. Body weight was recorded on days 1 (prior to administration), 8 and 15 for each animal. On day 15, all animals were necropsied and macroscopic pathology findings recorded.

Statistics:

Statistical analysis is inappropriate for this study, as there was only one dose group.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths at the limit dose of 2000 mg/kg.

Mortality:

There were no premature deaths.

Clinical signs:

other: Clinical signs were confined to Day 2, comprising of: - hunched posture in all animals (Nos. 1 to 10) - piloerection in two male animals (Nos. 1 and 4) and - chromodacryorrhoea (snout), slight in degree, in one male animal (No. 1).

Gross pathology:

Necropsy of each animal did not reveal any macroscopic pathology findings.

Conclusions:

In view of the dermal LD50 > 2000 mg/kg bodyweight attained in the present study, its outcome does not necessitate any classification or labelling regarding acute dermal toxicity according to EU regulations (REGULATION (EC) 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

In both, the acute oral and the acute dermal toxicity studies with ADK STAB FP-800, all animals survived the limit dose of 2000 mg/kg b.w. Therefore, classification of ADK STAB FP-900L for acute oral or dermal toxicity is not required [REGULATION (EC) 1272/2008].

 

Non-classification of ADK STAB FP-900L by the inhalation route was justified by its low vapour pressure making the inhalation exposure of humans to any vapour phase of it unlikely. The liquid form is very viscous limiting its availability as inhalable aerosol.