Phosphorous acid, mixed 2,4-bis(1,1-dimethylpropyl)phenyl and 4-(1,1-dimethylpropyl)phenyl triesters

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20th January 2010 and 10th February 2010.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Due to technician error, the dermal reaction observations for four females on Day 4 and four males on Day 11 were not recorded. These deviations were considered not to affect the purpose or integrity of the study, as no evidence of dermal irritation was noted pre or post Day 4 for females or pre or post Day 11 for males.

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of GLP inspection: 15/09/09 Date of Signature on GLP certificate: 26/11/09

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of bis[2,4-bis(2-methylbutan-2-yl)phenyl] 4-(2-methylbutan-2-yl)phenyl phosphite and 2,4-bis(2-methylbutan-2-yl)phenyl bis[4-(2-methylbutan-2-yl)phenyl] phosphite and tris[4-(2-methylbutan-2-yl)phenyl] phosphite.

EC Number:

700-485-5

Cas Number:

939402-02-5

Molecular formula:

Mixture of 4 components, the molecular formulae of which are: C33 H45 O3 P, C38 H55 O3 P, C43 H65 O3 P and C48 H75 O3 P

IUPAC Name:

Reaction mass of bis[2,4-bis(2-methylbutan-2-yl)phenyl] 4-(2-methylbutan-2-yl)phenyl phosphite and 2,4-bis(2-methylbutan-2-yl)phenyl bis[4-(2-methylbutan-2-yl)phenyl] phosphite and tris[4-(2-methylbutan-2-yl)phenyl] phosphite.

Test material form:

liquid: viscous

Details on test material:

Description: clear colourless viscous liquid
Date received: 05 November 2009
Expiry date: 15 June 2010
Storage conditions: approximately 4°C in the dark under nitrogen

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: eight to twelve weeks of age.
- Weight at study initiation: at least 200g
- Fasting period before study: none
- Housing: individually in suspended solid-floor polypropylene cages
- Diet (e.g. ad libitum): 2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK ad libitum
- Water (e.g. ad libitum): mains drinking water ad libitum
- Acclimation period: At least 5 days under laboratory conditions, after health examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface.

In the absence of data suggesting the test material was toxic, one male and one female rat were initially treated with the test material at a dose level of 2000 mg/kg.

The calculated volume of test material, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body
surface area) using a graduated syringe. A piece of surgical gauze, approximately 10 cm x 8 cm in size, was placed over the treatment area and semi-occluded with a piece of self adhesive bandage. The animals were caged individually for the 24 hour exposure period. Shortly after dosing the
dressings were examined to ensure that they were securely in place.

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened
with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

As no mortalities were noted a further group of animals (four males and four females) was similarly treated with the test material at a dose level of 2000 mg/kg bodyweight to give a total of five males and five females. After the 24 hour contact period the bandages were carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material. These animals were returned to group housing for the remainder of the test period.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

Rationale: Dermal administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% confidence limits not reported.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Increased respiratory rate and/or hunched posture were noted in two animals. No other signs of systemic toxicity were noted. There were no signs of dermal irritation.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

Introduction: The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of OECD Guidelines for the Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008.

Method: Initially, two animals (one male and one female) were given a single, 24 hour, semi-occluded dermal application of the undiluted test material to intact skin at a dose level of 2000 mg/kg bodyweight. Based on the results of the initial test, a further group of eight animals (four males and four females) was similarly treated. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Results:

Mortality: There were no deaths.

Clinical Observations: Increased respiratory rate and/or hunched posture were noted in two animals. No other signs of systemic toxicity were noted.

Dermal Irritation:  There were no signs of dermal irritation.

Bodyweight: All animals showed expected gains in bodyweight over the study period.

Necropsy: No abnormalities were noted at necropsy.

Conclusion: 

The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg. bodyweight.