Isooctadecyl pivalate

Endpoint summary

Description of key information

Oral (OECD 401): LD50 > 5000 mg/kg bw 
Inhalation (OECD 436): LC50 > 5.3 mg/L (read-across)
Dermal (OECD 402): LD50 > 2000 mg/kg bw (read-across)

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:

3 - 9 Mar 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. The observation period was 6 days, few details were reported, the administration volume was unusually high, the analytical purity was not stated.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted Feb 1987

Deviations:

yes

Remarks:

observation period 6 days, few details reported, the administration volume was unusually high, analytical purity not reported

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

other: NMRI EOPS

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation:20 - 21 g (range)

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 40 mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 6 days
- Frequency of observations and weighing: observations of mortality and signs of toxicity were made 3 h after administration and daily thereafter; animals were weighed prior to dosing and prior to necropsy.
- Necropsy of survivors performed: yes

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality during the study period.

Clinical signs:

other: From 30 minutes until 1 hour after administration an unspecified number of the mice had closed eyes, were lethargic and had irregular breathing. No clinical signs of toxicity were observed during the rest of the 6-day observation period.

Gross pathology:

No substance-related findings were noted during the necropsy.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The avaialble information comprises an adequate and reliable (Klimisch score 2) study, 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

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.3 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: Source: CAS 10233-13-3

Clinical signs:

other:

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

Based on the results of the available acute inhalation toxicity study with the source substance CAS 10233-13-3, a LC50 value > 5.3 mg/L (air) was determined. Applying the read-across approach, similar results are expected for the target substance CAS 58958-60-4.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 1) study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Source: CAS 163961-32-8

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

Based on the results of the available acute dermal toxicity study with the source substance CAS 163961-32-8, a LD50 value > 2000 mg/kg bw was determined. Applying the read-across approach, similar results are expected for the target substance CAS 58958-60-4.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 2) study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for read-across

Data on the acute inhalation and dermal toxicity of Isooctadecyl pivalate (CAS 58958-60-4) are not available. The assessment of acute inhalation and dermal toxicity was therefore based on studies conducted with analogue (source) substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity

CAS 58958-60-4

The acute oral toxicity of Isooctadecyl pivalate was assessed in a study that was performed according a protocol similar to OECD guideline 401 and under GLP conditions (Evic-Ceba, 1993). 5 male NMRI EOPS mice were administered 5000 mg/kg bw test substance via the oral route. There was no mortality during the 6-day study period. From 30 minutes until 1 hour after administration an unspecified number of the mice had closed eyes, were lethargic and had irregular breathing, which was probably caused by the applied unusually high dose volume (4 mL/100 g) No other clinical signs of toxicity were observed during the rest of the 6-day observation period. The body weight gain was within the range that is normal for this strain and study type. No findings were reported during the macroscopic examination. The acute oral LD50 value is considered to be > 5000 mg/kg/bw.

Acute inhalation toxicity

CAS 10233-13-3

An acute inhalation study was performed with Isopropyl laurate according to OECD guideline 436 and under GLP conditions (acute toxic class method) (Notox, 2010). 3 male and 3 female Crl:WI(Han) rats were exposed to an analytical concentration of 5.3 ± 0.3 mg/L of the test substance for 4 hours, nose-only. An aerosol was generated by nebulization of the test substance using a nebulizer. There was no mortality during the exposure or within the 14-day observation period. Hunched posture was observed in all animals 1 and 3 hours after exposure. The body weight gain was within the range expected for rats of this strain and age. No abnormalities were found during the macroscopic post-mortem examination of the animals. The inhalatory 4-h LC50 value of Isopropyl laurate in Wistar rats was found to exceed 5.3 mg/L.

 

Acute dermal toxicity

CAS 163961-32-8 

An acute dermal toxicity (limit test) was performed with Fatty acids, C16-18 and C18-unsatd., branched and linear, Bu esters according to OECD guideline 402 and under GLP conditions (Safepharm, 2004). 2000 mg/kg bw of the undiluted test substance was applied to the shaved skin of 5 rats/sex for 24 h under semiocclusive conditions. After the exposure period, residual test substance was removed and the animals were observed for a period of 14 days. No mortality occurred. Male and female rats showed the expected gain in body weight throughout the study, with the exception of 1/5 females that had a boy weight loss the first week and then a body weight gain the second week. The necropsy and histopathological examination did not reveal any substance-related findings. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

Overall conclusion for acute toxicity

The reliable data available for the target and source substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 values were greater than the currently applied limit values and the LC50 value was the maximum attainable value. Therefore, as the available data did not identify any hazard for acute toxicity, Isooctadecyl pivalate is not considered to be hazardous following acute exposure.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Isooctadecyl pivalate, data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the target substance information and analogue read-across approach, the available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.