Reaction mass of 1,3-dioxane-5,5-dimethanol and 1,3-Propanediol, 2-(hydroxymethyl)-2-[(methoxymethoxy)methyl]-

Endpoint summary

Description of key information

An acute oral toxicity study is available for Polyol PX.

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:

May 1981- 04 Mar 1982 (report issue date)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was not performed to modern international (OECD, EC, EPA) test guidelines and no indication of GLP compliance has been made; however the species, housing conditions and route of administration of the test substance were all appropriate to the endpoint examined, and the level of detail in the report is judged sufficient to consider the results reliable.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Remarks:

: older proprietary study, pre-dates GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: AlPk

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Unit, Imperial Chemical Industries PLC, Pharmaceuticals Division, Alderley Park, Macclesfield, Cheshire.
- Age at study initiation: Not specified.
- Weight at study initiation: 120 - 240 g
- Fasting period before study: 16 - 20 hours
- Housing: The rats (a maximum of five per cage) were housed in suspended stainless steel cages (370mm length x 320mm width x 200mm
height). The floor and back of each cage were 12mm square stainless steel mesh; the sides were solid stainless steel and the front was polycarbonate (MAKROLON).
- Diet (e.g. ad libitum): The animals were fed ad libitum with BP PCD pellets.
- Water (e.g. ad libitum): The animals were allowed tap water ad libitum.
- Acclimation period: Not documented


ENVIRONMENTAL CONDITIONS
- Temperature (°C): maintained between 19 - 23ºC
- Humidity (%): approximately 50 - 60%
- Air changes (per hr): 24
- Photoperiod (hrs dark / hrs light): 12 hours light in each 24 hour period.


IN-LIFE DATES: From: Not reported.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5, 10, 30, and 50% (w/v) aqueous solutions.
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Not specified
- Lot/batch no. (if required): Not specified
- Purity: Not specified


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


DOSAGE PREPARATION (if unusual): Not indicated.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: N/A

Doses:

500, 1000, 3000, and 5000 mg/kg

No. of animals per sex per dose:

Two animals per sex per dose level were used.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days (until day 15 of test)
- Frequency of observations and weighing: Animals were observed for signs of systemic toxicity at least once between 30 and 90 minutes and again
after 4 and 6 hours and daily thereafter up to day 8. If signs of toxicity were seen on day 8 observations were made on day 11, otherwise no further
observations were necessary until day 15.
- Necropsy of survivors performed: Not reported
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Not reported.

Statistics:

Not reported.

Preliminary study:

No signs of systemic toxicity were observed in any animal at any of the dose levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality at any dose level

Mortality:

No animal deaths reported at any dose level.

Clinical signs:

other: No signs of systemic toxicity were observed in any animal.

Gross pathology:

Not reported.

Other findings:

Not reported.

None

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Polyol PX was determined to have an LD50 value to male and female rats in excess of 5000 mg/kg bw

Executive summary:

A study was conducted in 1981 at the laboratories of Imperial Chemical Industries PLC, Macclesfield, Cheshire, UK, to determine the acute toxicity of the test substance Polyol PX when a single dose was administered by oral gavage to SPF albino rats. The study

was not conducted to any OECD Test Guideline, (however it is equivalent to a OECD 401 design) and no claim of GLP compliance was made. Groups of two male and two female rats were used in the range of dose levels, 500, 1000, 3000 and 5000 mg/kg bw. The animals were observed on the day of dosing at least once between 30 and 90 minutes and again between 4 and 6 hours post dose, then daily thereafter up to Day 8. No signs of systemic toxicity were observed at any time in any animal at any of the dose levels. Therefore, it was concluded that Polyol PX has an LD50 value in excess of 5000 mg/kg bw in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The study was not GLP- or guideline-compliant, however the methodology and results are considered to be reliable.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

The acute toxicity of Polyol PX was determined in AlPk rats (Nixon, 1982). Groups of 2 male and 2 female rats were administered single doses, by gavage, of 500, 1000, 3000 and 5000 mg/kg. The rats were observed for 8 days after dosing. No signs of systemic toxicity were observed in any animal, and no deaths occurred. It was concluded that the oral LD50 of Polyol PX is greater than 5000 mg/kg bw.

 

Acute inhalation toxicity

 

A waiver is proposed for this endpoint in accordance with Column 2 of Annex VIII of the REACH Regulation as inhalation is not considered to be a relevant route of exposure based on the physicochemical properties of the substance.

 

Acute dermal toxicity

 

A study is not required; a waiver is proposed according to Column 2 of Annex VIII of the REACH Regulation. No treatment-related effects were seen in an acute oral toxicity performed with the substance at dose levels of up to and including 5000 mg/kg bw. It can therefore be concluded that the substance is of inherently low acute toxicity. The study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation).Testing of the substance is therefore not considered to be scientifically justified and additionally cannot be supported on grounds of animal welfare.

Justification for selection of acute toxicity – oral endpoint
Single study available for this endpoint

Justification for classification or non-classification

Polyol PX was determined to have an LD50 value in male and female rats in excess of 5000 mg/kg bw. No data are available for acute inhalation toxicity, however this is not considered to be a relevant route of exposure. Based on the results of the acute oral toxicity study, very low acute dermal toxicity is also predicted. For the Reaction mass of 1,3 -propanediol, 2-(hydroxymethyl)-2-[(methoxymethoxy)methyl]- and 1,3-dioxane-5,5-dimethanol no classification is required according to EC Regulation 1272/2008.