Reaction Products of Dimethyl hydrogen phosphite and Alcohols C14-18, Even, Linear

Endpoint summary

Description of key information

The acute oral median lethal dose (LD50) of the test material in the Sherman-Wistar strain rat was found to be greater than 32 mL/kg bodyweight (equivalent to 8 g/kg).
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

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

Study period:

02 March 1974 to 18 April 1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Pre-GLP study

Qualifier:

no guideline available

Principles of method if other than guideline:

Five groups of 5 male fasted animals was given a single oral dose of test material as a solution in Corn Oil at dose levels of 2.0 mL/kg, 4.0 mL/kg, 8 mL/kg, 16.0 mL/kg and 32.0 mL/kg The animals were observed for fourteen days after the day of dosing.

GLP compliance:

no

Remarks:

Prior to GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sherman-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Test Animals
- Weight at study initiation - 200 to 250g
- Fasting period before study - 24 hours prior to dosing
- Diet - With the exception of an 24 hour fast prior to dosing, free access to food and water was allowed through the study

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% w/v suspension

MAXIMUM DOSE VOLUME APPLIED: 32ml/kg

:

Doses:

2.0 ml/kg
4.0 ml/kg
8.0 ml/kg
16.0 ml/kg
32.0 ml/kg

No. of animals per sex per dose:

5 males

Control animals:

no

Details on study design:

The animals were observed for signs of toxicity and mortality daily for 14 days.

Statistics:

No statistical analysis was performed.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 32 mL/kg bw

Based on:

test mat.

Mortality:

No deaths occured during the course of the study

Clinical signs:

No data

Body weight:

No data

Gross pathology:

No data

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: Section 1500.3 - Hazardous Substances and Articles, Administraton and Enforcement Regulations, Federal Register, Vol. 38 No 187 P.27014, 27 September 1973, Section (c) (2) (1)

Conclusions:

The Acute Oral LD50 in the male Sherman-Wistar rat was found to be greater than 32 mL/kg (equivalent to 8 g/kg)

Executive summary:

Guideline

A study was performed to assess the acute oral toxicity of the test material in the Sherman-Wistar strain rat.

Method

Five groups of 5 male fasted animals was given a single oral dose of test material as a solution in Corn Oil at dose levels of 2.0 mL/kg, 4.0 mL/kg, 8.0 mL/kg, 16.0 mL/kg and 32.0 mL/kg The animals were observed for fourteen days after the day of dosing.

Results

There were no deaths. The acute oral median lethal dose (LD50) of the test material in the Sherman-Wistar strain rat was found to be greater than 32 mL/kg bodyweight.

Conclusion

The Acute Oral LD50 in the male Sherman-Wistar rat was found to be greater than 32 mL/kg (equivalent to 8 g/kg).

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:

Between 27 November 2014 to 11 December 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Compliant Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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
- Source: Harlan Laboratories UK Ltd., Oxon UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: Males 271 to 287g, Females 201 to 222g
- Housing: in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): Teklad Gloabl Rodent Diet. ad libitum
- Water (e.g. ad libitum): Mains drinking water ad libitum



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light):12 hours continuous light and 12 hours darkness

IN-LIFE DATES: 27 November 2014 to 11 December 2014

Type of coverage:

semiocclusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: 10%
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occlued with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing ): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil to remove any residual test material
- Time after start of exposure: 24 hours

Duration of exposure:

24 hour

Doses:

Single dose level of 2000mg/kg

No. of animals per sex per dose:

Five males and Five females dosed at 2000mg/kg/bw

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. 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
- Other examinations performed: gross pathological examination, clinical observations, body weight, dermal reaction

Statistics:

No statistical analysis was performed

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the course of the study

Clinical signs:

There were no signs of systemic toxicity during the study

Body weight:

Animal showed expected gains in body weight except for one female which showed no gain during the first week but expected gain in body weight in the second week.

Gross pathology:

No abnormalities were noted at necropsy

Other findings:

There were no dermal effects on any of the animals

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethal dose LD50 of the test item after a single dermal application of both sexes is greater than 2000mg/kg body weight.

Executive summary:

Guideline

A study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24

February 1987) and Method 83 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Method

A group of ten animals (five males and five females) was given a single 24-hour, semioccluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then

killed for gross pathological examination.

Results

There were no deaths. No signs of systemic toxicity were noted during the study. No signs of irritation noted during the study.

All animals showed expected bodyweight gain during the study. No abnormalities were noted at necropsy.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Oral

A key study was performed to assess the acute oral toxicity of the test material in the Sherman-Wistar strain rat. Five groups of 5 male fasted animals was given a single oral dose of test material as a solution in Corn Oil at dose levels of 2.0 mL/kg, 4.0 mL/kg, 8.0 mL/kg, 16.0 mL/kg and 32.0 mL/kg The animals were observed for fourteen days after the day of dosing. There were no deaths. The acute oral median lethal dose (LD50) of the test material in the Sherman-Wistar strain rat was found to be greater than 32 mL/kg bodyweight (equivalent to 8 g/kg).

Inhalation

According to REACH Annex XIII Section 8.5 information on acute toxicity will be provided for at least one other route in addition to the oral route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. The substance is a waxy solid with a vapour pressure of 0.323 Pa at 25°C and, based on evaluation of the life cycle of the substance, it is concluded that inhalation exposure will be low and that the most likely route of exposure for workers and consumers is the dermal route. Testing for acute toxicity via the inhalation route is, therefore, not required.

Dermal

A study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method 83 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

A group of ten animals (five males and five females) was given a single 24-hour, semioccluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then

killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study. No signs of irritation noted during the study. All animals showed expected bodyweight gain during the study. No abnormalities were noted at necropsy. 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.

Justification for selection of acute toxicity – oral endpoint
Pre-GLP study providing acceptable description of experimental conditions.

Justification for selection of acute toxicity – dermal endpoint
GLP guideline study

Justification for classification or non-classification

The data showed no evidence of acute toxicity by either the oral or dermal route. The substance is not classified for acute toxicity.