Diethyl [[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methyl]phosphonate

Endpoint summary

Description of key information

The acute oral toxicity study in rats was revealed an LD50 value of >7750 mg/kg bw. In an acute dermal toxicity study conducted on rabbits the LD50 value was found to be greater than 5000 mg/kg bw.

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-Geigy Ltd., Basle, Switzerland
- Weight at study initiation: 160-180 g
- Housing: in groups of 5 in Macrolon cages (type 3)
- Fasting period before study: overnight
- Diet: ad libitum rat food
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 1 °C
- Humidity: 55 +/- 5 %
- Photoperiod (hrs dark / hrs light): 14/10

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 %
Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Doses:

4640 mg/kg bw, 6000 mg/kg bw, 7750 mg/kg bw (highest dose possible)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 750 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. The animals recovered within 8 to 13 days.

Gross pathology:

No substance related gross organ changes were seen.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test item in rats of both sexes observed over a period of 14 days is greater than 7750 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

7 750 mg/kg bw

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult animals
- Weight at study initiation: average body weight of about 3 kg
- Housing: single housing
- Diet: standard rabbit food ad libitum
- Water: ad libitum
- Acclimation period: 7 days

Type of coverage:

occlusive

Vehicle:

water

Remarks:

50% aqueous suspension

Details on dermal exposure:

TEST SITE
- Area of exposure: about 10 % of the total body surface area
- Type of wrap if used: impervious plastic sheeting
- Preparation of test site: The backs of the rabbits were shaved free of hair with electric clippers, the shaved area constituting about 10 % of the total body surface-area. Additionally, epidermal abrasions were made every 2 or 3 centimeters longitudinally over the area of exposure on one female and one male animal.

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: after removing of the wrap

TEST MATERIAL
- Amount applied: 5 g/ kg bw
- Concentration: 50 % (w/v) aqueous suspension
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing: before application, on day 8 and on day 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: none

Gross pathology:

no findings

Scarified and unscarified rabbits gave indistinguishable results.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Additional information

Acute oral toxicity

To assess the acute oral LD50 of the test compound, a test on rats was conducted. The test substance, suspended in polythylenglycole (30 %), was administered by gavage (concentrations: 4640, 6000, 7750 mg/kg body weight) to rats (5 per sex per dose). 7750 mg/kg body weight was the highest concentration possible. The animals were observed over a period of 14 days. No mortality occurred. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnea, exophthalmos, curved position and ruffled fur. The animals recovered within 8 to 13 days. No substance related gross organ changes were seen at autopsy. On the basis of this study, the LD50 value was determined to be greater than 7750 mg/kg body weight.

Acute dermal toxicity

An acute dermal toxicity test was conducted on rabbits. The test material concentration used was 5000 mg/kg body weight, which was the highest concentration possible to apply. Twenty-four hours before dermal application, the backs of the rabbits were shaved free of hair with electric clippers, the shaved area constituting about 10 % of the total body surface-area. Each dose-level group consisted of 2 male and 2 female rabbits. Immediately before application 1 male and 1 female were further prepared by making epidermal abrasions every 2 or 3 centimeters longitudinally over the area of exposure; the abrasions were sufficiently deep to penetrate the stratum corneum, but not to cause bleeding. After each application the exposure site was covered by wrapping the trunk with an impervious plastic sheeting securely taped in place to ensure intimate contact of epidermis and test material. The test material remained in contact with the skin for 24 hours, when the binders were removed, and an estimate of the volume of unabsorbed material made. The animals were thoroughly cleaned, and the exposure sites examined for local reactions. Observations for mortality, local reactions, and behavioral abnormalities were continued for a total period of 14 days following the skin applications. Gross autopsies were made on all animals, terminal body weights being recorded. As a result, scarified and unscarified animals gave indistinguishable results. No mortality was observed. Behavior was normal, and there was neither erythema nor edema; nothing unusual at autopsy. The LD50 was determined to be greater than 5000 mg/kg body weight.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008 (CLP). As a result the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No 1272/2008.