[No public or meaningful name is available]

Endpoint summary

Description of key information

Not toxic by the oral or dermal routes of exposure

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

1958

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

An analogue approach is used for the hazard assessment of several human health endpoints. The hypothesis for the analogue approach is that data can be read-across from data-rich substances, namely acetyl tributyl citrate (ATBC, CAS 77-90-7), acetyl triethyl citrate (CAS 77-89-4) and triethyl citrate (TEC, CAS 77-93-0) to acetyl trihexyl citrate (ATHC, CAS 24817-92-3). The analogue approach is based on common breakdown products via physical and biological processes, and similar functional groups, according to Annex XI, Section 1.5, of Regulation EC No. 1907/2006. Read-across to ATHC is indicated in order to avoid unnecessary in vivo testing according to Article 25 of Regulation EC No. 1907/2006.
The analogue approach to evaluating the safety of triethyl citrate is adopted here, reflecting the approach used by various expert panels and authoritative bodies in their safety assessment of TEC, included JECFA, EFSA, U.S. FDA, EPA and CIR. The use of analogues for hazard evaluation is justified (Scenarios 1 and 2 of the RAAF, 2015) because the substances have common breakdown products via physical and biological processes, which reflects the similar functional groups in their chemical structure. The proposed analogues have similar functional groups, including: a citric acid (tricarboxylic acid) backbone, three short-chain alkyl esters, and an acetyl group (except for TEC). Other than the acetyl group, there are no other functional groups which may introduce additional toxicities. The substances display similar classification based on similar toxicities.
The target substance is expected to have essentially the same effect in the toxicity test/endpoint as does the source substance. Dose descriptors obtained for derivation of a DNEL are adequate and appropriate, and do not underestimate the hazards of the registered substance.
This information is adequate to fulfill the data requirements of Annex IX, to be the basis for classification and labelling decisions, and for risk assessment.

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline available

Principles of method if other than guideline:

Predates establishment of OECD guideline and GLP. Standard acute oral gavage dosing of rats with 21 day observation period.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

not specified

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

Administered via oral gavage at 10-30 ml/kg bw.

Doses:

10 - 30 g/kg bw, equivalent to 10,000 to 30,000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

Observation for 21 days after dosing

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Remarks:

LD50 may be as high as 30000 mg/kg bw

Mortality:

No deaths

Clinical signs:

other: Leakage of the material from the rectum. Animals appeared somewhat sluggish but recovered promptly, showing no signs suggesting systemic toxicity in the ensuing 3 weeks.

Interpretation of results:

GHS criteria not met

Conclusions:

In a study of acute oral toxicity in 5 Wistar rats, the analogue test material was given via gavage at doses between approximately 10,000 and 30,000 mg/kg bw. No lethality or toxicity was observed. The LD50 is > 10,000 mg/kg bw. These data are applicable to the target substance, and are adequate for the purposes of risk assessment and classification and labeling

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 000 mg/kg bw

Quality of whole database:

adequate

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Judged to be scientifically reliable and appropriate for risk assessment by the Expert Panel of dermatologists and scientists at the Cosmetics Ingredient Review, Washington, DC., U.S.A.

Qualifier:

according to guideline

Guideline:

other: 16 CFR 1500.3

Version / remarks:

compliant with U.S. CPSC

Principles of method if other than guideline:

This summary data provided in a peer-reviewed publication reflects the opinion of the CIR Expert Panel that the test data are valid and informative. The study was commissioned by the Cosmetics, Toiletries and Fragrance Association (CTFA), now the Personal Care Products Council (PCPC), which generally selects OECD-compliant protocols (or FDA protocols which are aligned with OECD guidelines) and requires execution of the study under GLP.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Purity > 99% ATHC, Volatiles 1.4%.

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

Female albino rabbits were divided equally into two groups (intact and abraded test sites, respectively). The mean body weight was 2.29 for one group (intact) and 2.81 kg (abraded sites) for the other group.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Skin in one group of animals is abraded, skin of the other group is intact. The test material is applied on gauze and covered with an occlusive dressing for 24 h.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw (2 g/kg).

No. of animals per sex per dose:

5 per sex per dose

Control animals:

not required

Details on study design:

The animals are observed after the application and at least once daily. The obsrvation period is 14 days. Animals are euthanised at 14 days, and necropsied are undertaken.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No dealths occurred.

Clinical signs:

other: No clinical signs of systemic toxiicty.

Gross pathology:

No changes were observed in any of the animals tested.

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance was tested in an acute dermal toxicity study in 10 male/female rabbits at doses of 2000 mg/kg bw. Within the 14-day observation period, there were no deaths or clinical effects among the animals. The LD50 is > 2000 mg/kg bw. The substance does not meet the criteria for classification for acute oral toxicity according to Regulation EC No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

adequate

Justification for classification or non-classification

In oral and acute dermal acute toxicity tests, the substance showed LD50s > 2000 mg/kg bw. The substance does not meet the criteria for classification for acute toxicity under Regulation EC No. 1272/2008.