Tris(methylphenyl) phosphate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 4 1979 to February 22 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP study, no specific methodology followed although fully documented report available.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute dermal toxicity in rabbits was determined according to the procedures suggested by Hagan. New Zealand white rabbits were assigned to groups and maintained under standard laboratory conditions prior to administration of the test material.

Prior to determination of LD50 , single animals were dosed at various levels to determine a range within which the LD50 could be determined. The animals were prepared by clipping the skin of the mid-dorsal area of the trunk free of hair. Animals were further prepared by introducing longitudinal epidermal incisions over the clipped skin surface, thus enhancing the penetrability of the stratum corneum. Applications were made under gauze patches. The dosed area was then covered with an impermeable p lastic wrapping for 24 hours, after which it was removed and the skin gently cleansed.

Animals were returned to quarters where food and water were available ad libitum following the dose application, and were observed fourteen full days following application to determine mortality during this period.

Following the range finding, rabbits were divided into groups of six , sexes equally distributed, one-half of the animals abraded. Groups were dosed, as described above, at graded dose levels according to the results of the range finding previously performed.

Animals were observed for signs of pharmacologic activity and drug toxicity at 1, 3, 6, and 24 hours post-dosage. Observations were made daily thereafter for a total of fourteen days. Non-surviviors and animals sacrificed a t the end of the 14 day observation period were subjected to complete gross necropsy. LD50 together with 95% confidence limits was determined, where possible, by the method of Litchfield and Wilcoxin.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Kronitexs TCP, C-8824-29

IUPAC Name:

Kronitexs TCP, C-8824-29

Details on test material:

- Name of test material (as cited in study report): Kronitex TCP, C-8824-29
- Molecular formula (if other than submission substance): Not applicable
- Molecular weight (if other than submission substance): Not applicable
- Smiles notation (if other than submission substance): Not specified
- InChl (if other than submission substance): Not specified
- Structural formula attached as image file (if other than submission substance): see Fig. No
- Substance type: Not specified
- Physical state: Not specified
- Analytical purity: Not specified
- Impurities (identity and concentrations): Not specified
- Composition of test material, percentage of components: Not specified
- Isomers composition: Not specified
- Purity test date: Not specified
- Lot/batch No.: Not specified
- Expiration date of the lot/batch: not specified
- Radiochemical purity (if radiolabelling): not applicable
- Specific activity (if radiolabelling): not applicable
- Locations of the label (if radiolabelling): not applicable
- Expiration date of radiochemical substance (if radiolabelling): not applicable
- Stability under test conditions: not specified
- Storage condition of test material: not specified
- Other:

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

All animals are fed and watered ad libitum; with Wayne animal feeds used exclusively. Animals are received from Summit View Farm, Belvidere, New
Jersey and are conditioned prior to use.
Rabbits were divided into groups of six , sexes equally distributed, one-half of the animals abraded.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

not specified

Remarks:

Presumably neat.

Details on dermal exposure:

The animals were prepared by clipping the skin of the mid-dorsal area of the trunk free of hair. Animals were further prepared by introducing longitudinal epidermal incisions over the clipped skin surface, thus enhancing the penetrability of the stratum corneum. Applications were made under
gauze patches. The dosed area was then covered with an impermeable plastic wrapping for 24 hours, after which it was removed and the skin gently cleansed.

Duration of exposure:

24 h

Doses:

Single doses, at 3.14, 5, 6.3, 10, 12.6 g/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Acute dermal toxicity in rabbits was determined according to the procedures suggested by Hagan (1959). New Zealand white rabbits were assigned to groups and maintained under standard laboratory conditions prior to administration of the test material.
Prior to determination of LD50 single animals ere dosed at various levels to determine a range within which the LD could be determined.
The animals were prepared by clipping the skin of the mid-dorsal area of the trunk free of hair. Animals were further prepared by introducing longitudinal epidermal incisions over the clipped skin surface, thus enhancing the penetrability of the stratum corneum. Applications were made under
gauze patches. The dosed area was then covered with an impermeable plastic wrapping for 24 hours, after which it was removed and the skin gently cleansed. Animals were returned to quarters where food and water were available ad libitum following the dose application, and were observed fourteen full days following application to determine mortality during this period.
Following the range finding, rabbits were divided into groups of six , sexes equally distributed, one-half of the animals abraded. Groups were dosed, as described above, at graded dose levels according to the results of the range finding previously performed. Animals were observed for signs of pharmacologic activity and drug toxicity at 1, 3, 6, and 24 hours post-dosage. Observations were made daily thereafter for a total of fourteen days. Non-survivors and animals sacrificed at the end of the 14 day observation period were subjected to complete gross necropsy. LD50 together with 95% confidence limits was determined where possible, by the method of Litchfield and Wilcoxin (1949).

Statistics:

None specified.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3.7 other: g/kg

Based on:

test mat.

95% CL:

2.31 - 5.92

Mortality:

Range finding study: 2 animals at 10.0 and 15.0 g/kg dose levels were found dead on Day 2.

Full study:
Dose level: 3.14 g/kg: No deaths
Dose level: 5.00 g/kg: 2 deaths were noted on Day 3. 1 death occured on Day 5.
Dose level: 6.30 g/kg: 2 deaths were noted on Day 4. 1 death occured on Day 5. Animal 6 died on Day 10 and was replaced.
Dose level: 10.00 g/kg: Deaths were noted on Days 2,3,4,5 and Day 9 (unspecified)
Dose level: 12.60 g/kg: 1 death was noted on Day 2; 2 deaths were noted on Day 3. 2 deaths were noted on Day 4.

Clinical signs:

other: Dose level: 3.14 g/kg: Skin pliable and non - irritated. No gross changes observed. Animal 3, on days 4 - 6: Possible respiratory infection - slight difficulty breathing. Dose level: 5.00 g/kg: Skin pliable and non - irritated ; faeces loose. No gross

Gross pathology:

No pathological findings were recorded.

Any other information on results incl. tables

Table 1

	Dose level g/kg	Sex	Dead/dosed	% Mortality
Range finding	1.00	1M	0/1	0
	5.00	1M	0/1	0
	10.00	1F	1/1	100
	15.00	1F	1/1	100
Test dosage	3.14	3M:3F	0/3:0/3	0
	5.00	3M:3F	2/3:2/3	67
	6.30	3M:3F	2/3:2/3	67
	10.00	3M:3F	3/3:2/3	83

 

LD50 = 3.7 (2.31 - 5.92) g/kg

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal toxicity of Tricresyl Phosphate (LD50) is 3.7 (2.31 - 5.92) g/kg

Executive summary:

The study has shown the acute dermal toxicity of Tricresyl Phosphate (LD50) to be 3.7 (2.31 - 5.92) g/kg. No classification is applicable.