1,2,3-Propanetriol, mono- and diformates

Endpoint summary

Description of key information

Oral: LD50 (guinea pig, m/f) = 390 mg/kg bw (lowest dose descriptor available)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given. Lack of test material details and no individual data. Read-across from analogous substance. For details on read-across please refer to the attached read-across report.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Single oral administration by stomach tube in guinea pigs.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 250-300 g
- Diet: Purina chows, supplemented by fresh vegetables
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

other: 1% aqueous "Tergitol" penetrant 7 (sodium sulfate of heptadecyl alcohols)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: maximal concentration 5%

DOSAGE PREPARATION: The test material was insufficiently soluble to be fed in solution and was handled as temporary dispersion in 1% aqueous sodium sulfate of heptadecanol (trademarked "Tergitol" penetrant 7).

MAXIMUM DOSE VOLUME APPLIED: Individual dose levels were not reported for any of the substances tested including the test substance considered herein. According to the authors, the highest dose level which could safely be hold at one time by the animal was just over 10% of the animal’s bodyweight, corresponding to approx. 50 g/kg bw, when a substance was administered as a 50% solution. This is equivalent to a dose volume of 100 mL/kg bw.
Furthermore, it was reported that in most cases 10 animals were dosed to determine the toxicity of a particular dosage and enough dosages were given to include those at which no mortality occurred and those at which all tested animals died.
The test substance was administered as a 5% dispersion in 1% aqueous sodium sulfate of heptadecanol (trademarked "Tergitol" penetrant 7) and based on the information above and the resulting LD50 value, it appears unlikely that the test substance could have been administered at a dose volume > 100 mL/kg bw.
It is therefore assumed that the maximum dose volume applied was 100 mL/kg bw corresponding to a maximum dose level of 5000 mg/kg bw.

Doses:

Not specified (presumably up to 5000 mg/kg bw)

No. of animals per sex per dose:

ca. 10 animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The data were calculated by the method of probits, described by Bliss C.I. (1935. The calculation of the dosage-mortality curve. Ann. Appl. Biol. 22:134-167).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

390 mg/kg bw

Based on:

test mat.

95% CL:

270 - 580

Remarks on result:

other: probit slope: 2.61

Mortality:

Mortality data were summarised for all substances tested. Therefore, no substance specific data were reported.
According to the authors, most deaths occurred within the first 48 h post-dose, but all deaths within 14 days post-administration were taken into account for calculation of LD50 values.

Clinical signs:

other: The test substance was tested along with other glycol esters. For this group, (near) fatal doses caused no narcosis but various degrees of sluggish depressed function.

Gross pathology:

Gross pathology findings were summarised for all substances tested. According to the authors, all doses caused some degree of irritation of the digestive tract. The primary target organ was the kidney; blood in urine and free blood beneath the capsule were seen at the highest dosages. The liver was less affected, but orange or reddish bile was often observed. Glycol esters were reported to produce livers of bright eosin colour.

Interpretation of results:

harmful

Remarks:

Migrated information Acute Oral 4, H302 Criteria used for interpretation of results: EU

Conclusions:

An LD50 of 390 mg/kg ethylene diformatewas reported in male and female guinea pigs. This result is used in a read-across approach in the assessment of 1,2,3-propanetriol, mono- and diformates.

Executive summary:

In an acute oral toxicity study, guinea pigs were given a 5000 mg/kg bw dose of ethylene diformate in 1% aqueous "Tergitol" penetrant 7 (sodium sulfate of heptadecyl alcohols) and observed for 14days.  The oral LD50 in males and females is 390 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

390 mg/kg bw

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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

Oral

No studies are available to assess the acute oral toxicity of 1,2,3-propanetriol, mono- and diformate. However, the structurally related substance ethylene diformate (and further glycol derivatives) was investigated in two early studies conducted in rats and guinea pigs (Smyth, 1941). Groups of ca 10 animals (male rats, male and female guinea pigs) were given the test substance as a 5% dispersion in 1% aqueous "Tergitol" penetrant 7 (sodium sulfate of heptadecyl alcohols) by single oral gavage. The dose levels administered were not explicitly reported, but it can be assumed that the maximum dose level was in the order of 5000 mg/kg bw. The observation period following administration was up to 14 days. Mortality data were summarised for all substances tested. Therefore, no substance specific data were reported. According to the authors, most deaths occurred within the first 48 h post-dose, but all deaths within 14 days post-administration were taken into account for calculation of LD50 values. The test substance was tested along with other glycol esters. For this substance group, (near) fatal doses caused no narcosis but various degrees of sluggish depressed function. Gross pathology findings were summarised for all substances tested. According to the authors, all doses caused some degree of irritation of the digestive tract. The primary target organ was the kidney; blood in urine and free blood beneath the capsule were seen at the highest dosages. The liver was less affected, but orange or reddish bile was often observed. Glycol esters were reported to produce livers of bright eosin colour. The calculated oral LD50 values for male rats and male/female guinea pigs were 1510 and 390 mg/kg bw, respectively. The substance is therefore considered to be harmful if swallowed.

Dermal and inhalation

Information on the acute dermal and inhalation toxicity of 1,2,3-propanetriol, mono- and diformates is not available.

Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study with the lowest dose descriptor.

Justification for selection of acute toxicity – inhalation endpoint
In accordance with column 2 of Annex VIII, section 8.5, of Regulation (EC) No 1907/2006, an acute inhalation toxicity study generally does not need to be conducted if the substance is classified as corrosive to the skin.

Justification for selection of acute toxicity – dermal endpoint
In accordance with column 2 of Annex VIII, section 8.5, of Regulation (EC) No 1907/2006, an acute dermal toxicity study generally does not need to be conducted if the substance is classified as corrosive to the skin.

Justification for classification or non-classification

Data on the acute oral toxicity of 1,2,3-propanetriol, mono- and diformates is not available. However, the structurally related substance ethylene diformate meets the classification criteria for Acute toxicity Category 4 (H302: Harmful if swallowed) according to Regulation (EC) 1272/2008 and for R22 (Harmful if swallowed) according to Directive 67/548/EEC. This classification is considered to be valid for 1,2,3-propanetriol, mono- and diformates.

No data are available on acute dermal or inhalation toxicity. The substance is, however, classified for skin corrosion (Category 1B). Therefore, acute toxicity studies do not need to be conducted. Risk management measures protecting against corrosive effects are considered to be adequate to prevent acute poisoning.