Didocosyl sebacate

Endpoint summary

Description of key information

Oral LD50 (OECD 420), rat > 2000 mg/kg bw 
Dermal LD50 (OECD 402), rat > 2000 mg/kg bw 

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:

19 Jul - 09 Aug 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

(2001)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

(2008)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: (RccHan:WIST)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK, Ltd., Oxon, UK
- Age at study initiation: 8 – 12 weeks
- Weight at study initiation: 163 – 177 g
- Fasting period before study: overnight before dosing
- Housing: Animals were caged in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: 2014C Teklad Global Rodent diet (Harlan Laboratories UK, Ltd., Oxon, UK), ad libitum
- Water: (tap/filtered) water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL
- Justification for choice of vehicle: Arachis oil was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not specified

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Frequency of weighing: prior to dosing and 7 and 14 days after treatment
- Necropsy of survivors performed: yes
- Other examinations performed: External appearance, body orifices, body cavities (thoracic and abdominal) and their contents were examined macroscopically

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortalities or clinical signs of toxicity observed

Mortality:

No mortalities were observed during the study.

Clinical signs:

No clinical sings were observed during the study.

Body weight:

All animals showed expected gains in bodyweight during the study period.

Gross pathology:

No abnormalities were noted at necropsy.

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, 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 adverse effect observed

Quality of whole database:

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

Additional information

Acute oral toxicity

A reliable key acute oral toxicity study performed according to OECD TG 420 and in compliance with GLP with Didocosyl sebacate (CAS 42233-75-0) is available (Sanders, A., 2012a). In this limit test five fasted female Wistar rats were administered one dose of 2000 mg/kg bw of the test substance (CAS 42233-75-0) via oral gavage. The animals were observed for 14 days post-administration. The acute oral LD50 value for females was calculated to be greater than 2000 mg/kg bw. No clinical signs of toxicity were reported, no mortalities occurred and all animals showed the expected body weight gains during the study period. In addition, no abnormalities were detected at necropsy at the end of the 14-day observation period. Based on the study results and according to EU classification criteria, the test substance is not to be classified.

 

Acute dermal toxicity

A key acute dermal toxicity study performed according to OECD TG 402 and in compliance with GLP with Didocosyl sebacate (CAS 42233-75-0) is available (Sanders, A., 2012b). In this limit test five Wistar rats of each sex were exposed to a single dose of 2000 mg/kg bw of the test substance for 24 h via semi-occlusive dressing and observed for 14 days post-application. The acute dermal LD50 value was calculated to be greater than 2000 mg/kg bw. No severe clinical signs of toxicity were reported and no mortalities occurred during the observation period. Red/brown staining around the snout was noted in one male, two and four hours post-application, but neither erythema nor edema was noted in any animal during the study period. Animals showed expected gains in bodyweight over the study period, except for one male and one female which showed bodyweight loss or no gain in bodyweight during the first week but expected gain in bodyweight during the second week. No abnormalities were detected at necropsy at the end of the 14-day observation period. Based on the study results and according to EU classification criteria, the test substance is not to be classified. According to Regulation (EC) No 1907/2006 Annex VIII, Section 8.5.2, Column 2, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely, taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. Didocosyl sebacate CAS (42233-75-0) is a white solid indicating to be composed of non-free flowing wax. The substance has a very low vapour pressure (<0.0013 Pa at 25 °C), which also indicates a low potential for exposure via inhalation. The proportion of the test item having an inhalable particle size of less than 100 µm was determined to be 0.134%. Therefore, during normal handling and use of the test material, it is considered to be essentially non-inhalable. In support dust generating properties of the substance were evaluated. On visual inspection the test item appeared to be composed of non-free flowing wax like flakes which were far too large to be generated into a suitable test atmosphere. In order to try and reduce the particle size of the test item and facilitate aerosolisation the test item was ground using a mini grinder prior to use, however, this had minimal effect on the test item, it was, therefore, ground using a Retsch Planetary Ball Mill (Retsch (UK) Ltd, Leeds, UK). This was also unsuccessful in reducing the particle size of the test item to a suitable level that would have allowed test atmosphere to be generated. As it proved impossible to reduce the particle size so as to generate a powder aerosol, it was considered appropriate to try and generate the test item as a liquid aerosol. This method had been successful when trying to generate difficult powders/solids as liquid aerosols in the past. Two solvents (Ethanol Absolut and Xylene) were chosen in order to try and dissolve the test item such that a suitable formulation could be produced. Neither of these solvents had any effect on the test item, further efforts to try and find solubility data for this test item were unsuccessful. In summary, due to the physical nature of the test item and its apparent low volatility, the registered substance is considered unlikely to represent a significant hazard by the inhalation route. In addition, the dust generation properties of the test material were shown to be low, it was, therefore, considered not to be possible to generate an inhalable aerosol from the test item in its´ original form or as a liquid formulation.

Justification for selection of acute toxicity – oral endpoint
The reliable GLP compliant OECD Guideline study was choosen.

Justification for selection of acute toxicity – dermal endpoint
The reliable GLP compliant OECD Guideline study was choosen.

Justification for classification or non-classification

The available data on acute toxicity of the registered substance do not meet the criteria for classification according to Regulation 1272/2008, and are therefore conclusive but not sufficient for classification.