Bis(16-methylheptadecyl) malate

Endpoint summary

Description of key information

Oral LD50 (OECD 401), mouse, LD50 >5000 mg/kg bw 
Dermal LD50 (OECD 402), rat, LD50 >2000 mg/kg bw (RA from CAS 149144-85-4)

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:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given. No data on test material purity and limited details on test animals and experimental conditions.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no data on test material purity and limited details on test animals and experimental conditions

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 20 g

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 males or females

Control animals:

no

Details on study design:

- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occurred during the study period.

Clinical signs:

other: No clinical signs and no behavioural abnormalities were observed after treatment with the test substance.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable studies (Klimisch score 2) from the target substance and from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products, similarities in PC/ECO/TOX properties. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

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:

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

Adequacy of study:

key study

Study period:

March - April 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Morini - S. Polo d'Enza (RE), Italy
- Weight at study initiation: 170 - 230 g
- Fasting period before study: not mentioned
- Housing: in groups of 5 per sex per cage (polycarbonate, dimensions 425x266x180 mm)
- Diet: standard pellet complete diet ad libitum
- Water: filtered tap water ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 55 +/- 15
- Air changes (per hr): 25
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29-MAR-1993 To: 12-APR-1993

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: no data

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: no data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL/kg

Duration of exposure:

no data

Doses:

2000 m/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: daily in the working week (5 out of 7 days)
Clinical symptoms (including evaluation of body functions, tegumentary apparatus, mucosae conditions, respiratory activity, somatomotor activity and sensorium conditions): daily in the working week (5 out of 7 days)
Body weight: before the experiment, at day 7 and 14
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Signs of toxicity related to dose levels: None

Gross pathology:

No pathological symptoms were observed, nothing abnormal was found.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products, similarities in PC/ECO/TOX properties. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for grouping of substances and read-across

There are only limited data available on acute toxicity of Diisooctadecyl malate (CAS 67763-18-2). In order to fulfil the standard information requirements set out in Annex VII and VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted. In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across). Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview on acute toxicity

CAS	Chemical name	Molecular weight [g/mol]	Acute toxicity Oral	Acute toxicity Inhalation	Acute toxicity Dermal
67763-18-2 (a)	Diisooctadecyl malate	639.06	Experimental result: LD50 >5000 mg/kg bw (mouse)   RA: CAS 149144-85-4	--	RA: CAS 149144-85-4
149144-85-4 (b)	Di C12-13 Alkyl Malate	470.73/498.78	Experimental result: LD50 >5000 mg/kg bw (rat)	--	Experimental result: LD50 >2000 mg/kg bw (rat)

(a) The substance subject to registration is indicated in bold font.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

The above mentioned substances are considered to be similar on the basis of the structural similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Diisooctadecyl malate (CAS 67763-18-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

Beside an acute oral toxicity study with Diisooctadecyl malate (CAS 67763-18-2) no further reliable data on acute toxicity is available with Diisooctadecyl malate (CAS 67763-18-2). Therefore, read across from the structurally analogue substance Di C12-13 Alkyl Malate (CAS 149144-85-4) was applied.

 

Acute toxicity: oral

CAS 67763-18-2

The acute oral toxicity study with Diisooctadecyl malate (CAS 67763-18-2) was conducted equivalent or similar to OECD TG 401 and in compliance with GLP (Dufour, 1988a). In this limit test five NMRI mice of unknown gender were administered one dose of 5000 mg/kg bw of the test substance (CAS 67763-18-2) via oral gavage. The acute oral LD50 value was calculated to be greater than 5000 mg/kg bw. No signs of clinical toxicity were reported, no mortalities occurred during the observation period. Based on the study results and according to EU classification criteria, the test substance is not to be classified.

CAS 149144-85-4

The acute oral toxicity study with Di C12-13 Alkyl Malate (CAS 149144-85-4) was conducted according to OECD TG 401 and in compliance with GLP (Biffi, 1992). The test substance was administered at a limit dose of 5000 mg/kg by using a stomach tube. There were no cases of mortality during the study period. In summary, 3/10 rats showed piloerection from day 1 to 3. The body weight gain was normal during the study period. At the necropsy all animals showed slightly reddened gastric mucosa. The LD50 value was calculated to be greater than 5000 mg/kg bw and he test substance was found to be non-toxic under the experimental conditions.

Based on the above study results with Diisooctadecyl malate (CAS 67763-18-2) and the read across substance Di C12-13 Alkyl Malate (CAS 149144-85-4) and according to EU classification criteria, the test substance Diisooctadecyl malate is not to be classified.

 

Acute toxicity: dermal

CAS 149144-85-4

The test for acute dermal toxicity was performed on a group of ten rats (5 male and 5 female) according to EU Method B.3 and in compliance with GLP (Biffi, 1993a). The test substance Di C12-13 Alkyl Malate (CAS 149144-85-4) was administered at a limit dose of 2000 mg/kg bw by dermal application. During the study period no mortality occurred. Furthermore, no clinical symptoms were observed during the study period and the body weight gain was normal for the used species. At necropsy the animals showed no pathological symptoms. Therefore, the LD50 value was calculated to be greater than 2000 mg/kg bw and the test substance was found to be non-toxic under the experimental conditions. Based on the results of the study and according to EU classification criteria, the test substance is not to be classified.

Acute toxicity: inhalation - Waiving

The substance has very low vapour pressure, so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Furthermore the results of laboratory animal studies show low acute oral and dermal toxicity for the substance. This intrinsic property/toxicity potential can be extrapolated to acute inhalative route administration.

Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment.

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 Diisooctadecyl malate (CAS 67763-18-2), 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 acute oral toxicity study and the 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.