(R,R)-(-)-butane-2,3-diol

Endpoint summary

Description of key information

Oral: The acute oral LD50 was determined to be > 5000 mg/kg bw in rats.

Inhalation: No mortality was observed in an inhalation risk test with a saturated vapor (LD50 > 0,85 mg/l) in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979-04-18 - 1980-12-22

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Method: other: BASF test

GLP compliance:

no

Test type:

other: BASF test

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality

Clinical signs:

other: Dyspnea, Apathy, Staggering, Piloerection, Erythema, Exophthalmos, Poor general state

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the available data the substance showed no mortality up to 5000 mg/kg bw.

Executive summary:

Based on the available data the substance showed no mortality up to 5000 mg/kg bw. Clinical signs were dyspnoea, apathy, staggering, piloerection, erythema, exophthalmos, and a poor general state.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details on endpoint specific justification please refer to the read-across report, endpoint specific justification.

Reason / purpose for cross-reference:

assessment report

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Effect conc. are identical for the submission substance, because target and source substance have the same MW.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the available data the substance showed no mortality up to 5000 mg/kg bw.

Executive summary:

The study used as source investigated acute toxicity (oral) to rat. The study results of the source compound were considered applicable to the target compound, and were used for classification and labelling acc. to Regulation (EC) No 1272/2008. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

23 January 2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

QSAR predictions for oral toxicity:
- T.E.S.T. 4.2.1
- ProTox II - oral toxicity
- Danish (Q)SAR Database

Qualifier:

no guideline required

GLP compliance:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 380 mg/kg bw

Based on:

test mat.

QSAR prediction results for oral toxicity:

- T.E.S.T. 4.2.1:

LD50: 3380 mg/kg

Predicted Toxicity Class: 5

Average similarity: 100%

Prediction accuracy: 100%

- ProTox II - oral toxicity

Oral rat LD50: 7966.76 mg/kg

Predictions for the test chemical and for the most similar chemicals in the external test set

Mean absolute error in -Log10(mol/kg): Similarity coefficient ≥ 0.5; i.e. 0.42

Mean absolute error in -Log10(mol/kg): Entire set 0.43

Predictions for the test chemical and for the most similar chemicals in the training set

Mean absolute error in -Log10(mol/kg): Similarity coefficient ≥ 0.5; i.e. 0.34

Mean absolute error in -Log10(mol/kg): Entire set 0.34

- Danish (Q)SAR Database

Acute toxicity in Rodents

ACDLabs

LD50 (mg/kg/d)

Reliability Index

Rat Oral

9900

0.77

Rat Intraperitoneal

3300

0.75

Mouse Oral

10000

0.65

Mouse Intraperitoneal

3700

0.61

Mouse Intravenous

1400

0.57

Mouse Subcutaneous

2900

0.55

Reliability index: <0.3 = Not reliable prediction quality; 

0.3-0.5 = borderline prediction quality;

0.5-0.75 = moderate prediction quality;

>0.75 = high prediction quality.

Interpretation of results:

GHS criteria not met

Conclusions:

2,3-BUTANEDIOL (L) is not acute toxic via the oral route, i.e. the predicted LD50 (oral, rodent) >= 3380 mg/kg/d.

Executive summary:

Predicted results of models T.E.S.T. 4.2.1, ProTox II - oral toxicity and the Danish (Q)SAR Database indicated unambiguously that the test item is of no or very low acute toxicity to humans, i.e. the predicted LD50 (oral, rodent) >= 3380 mg/kg/d.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

sufficient for evaluation

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

Method: other: BASF test

GLP compliance:

no

Test type:

other: inhalation risk test (IRT)

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

7 h

Concentrations:

saturated atmosphere (20°C); max 0.85 mg/l

No. of animals per sex per dose:

a total of 12 animals

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.85 mg/L air

Based on:

other: saturated atmosphere of the test item

Interpretation of results:

GHS criteria not met

Executive summary:

No mortality was observed when 12 rats were exposed for 7 h to an atmosphere that has been saturated at 20°C with the volatile part of the compound.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For details on endpoint specific justification please refer to the read-across report, endpoint specific justification.

Reason / purpose for cross-reference:

assessment report

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.85 mg/L air

Based on:

other: saturated atmosphere of the test item

Remarks on result:

other: Effect conc. are identical for the submission substance, because target and source substance have the same MW.

Interpretation of results:

GHS criteria not met

Conclusions:

No mortality was observed when 12 rats were exposed for 7 h to an atmosphere that has been saturated at 20°C with the volatile part of the compound.

Executive summary:

The study used as source investigated acute toxicity (inhalation) to rat. The study results of the source compound were considered applicable to the target compound, and were used for classification and labelling acc. to Regulation (EC) No 1272/2008. Justification and applicability of the read-across approach (structural analogue) is outlined in the read-across report in section 13.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

850 mg/m³ air

Quality of whole database:

sufficient for evaluation

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No key study is available on acute toxicity for the submission substance. However, adequate and reliable data are reported here for a structural analogue (source substance 2,3 -butandiol). Please also refer to the read-across justification document.

Oral

In the available key study, the test article 2,3 -butandiol was administered to 10 rats (5 male and 5 female). Observation period was 14 days. The oral LD50 was determined to be > 5000 mg/kg bw. Clinical signs observed were dyspnoea, apathy, staggering. [BASF 1980].

In a supporting study performed with the submission substance, predicted results of models T.E.S.T. 4.2.1, ProTox II - oral toxicity and the Danish (Q)SAR Database indicated unambiguously that the test item is of no or very low acute toxicity to humans, i.e. the predicted LD50 (oral, rodent) >= 3380 mg/kg/d.

Inhalation

In the available key study, no mortality was observed when 12 rats were exposed for 7 h to an atmosphere that has been saturated at 20°C with the volatile part of the compound (LC50 > 0,85 mg/l) [BASF, 1980]. 

Justification for classification or non-classification

No classification and labelling for acute oral and inhalation toxicity is necessary according to the CLP regulation.