Docosyl stearate

Endpoint summary

Description of key information

Oral (OECD 423): LD50 (female, rat) > 2000 mg/kg bw

Dermal (OECD 402): LD50 (male/female, rat) > 2000 mg/kg bw (read-across from CAS 3687-46-5, key)

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:

23 Sep - 08 Dec 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted Dec 2001

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Remarks:

SPF [Crl:CD(SD)]

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Atsugi Breeding Center, Charles River Laboratories Japan Inc, Japan
- Age at study initiation: 8 weeks
- Weight at study initiation: 197 - 203 g (range)
- Fasting period before study: Yes, approximately 18 h overnight
- Housing: 2 or 3 animals per cage were housed in plastic solid-floored cages (W 440 x D 275 x H 180 mm; by Hanyu Seimitsu Inc.) with bedding (ALPHA-dri, Shepherd Specialty Papers, Inc., Lot Nos: 04116 and 05116).
- Diet: CR -LPF pelleted diet (irradiation-sterilized, Oriental Yeast Co., Ltd., Lot No.: 160621), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: Animals were quarantined/acclimated to the test environment for over a week at the testing facility.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 39 - 48
- Air changes (per hr): 10 -15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 Sep 2016 To: 08 Dec 2016

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Since the acute oral toxicity of the test substance was expected to be low, the starting dose level was set at 2000 mg/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 (first and second step, respectively)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed frequently for the first 6 hours after administration (from immediately after administration to 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 6 hours after administration), and once daily thereafter for 14 days, for clinical signs such as abnormalities of external appearance, nutritional condition, posture, behavior and excretions. Body weight was recorded on day 0 of administration and on days 1, 3, 7 and 14 after administration.
- Necropsy of survivors performed: Yes, all animals were sacrificed after the 14-day observation period by exsanguination via the abdominal aorta under isoflurane anesthesia and necropsied. External appearance and organs/tissues in the cranial, thoracic and abdominal cavities were examined macroscopically.

Statistics:

For body weight, the mean value with standard deviation was calculated for each point measured for each dose step. The body weight gain during the observation period from day 0 of administration to day 14 after administration was determined and the mean value with standard deviation was calculated in the same manner.

Key result

Sex:

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: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

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

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

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

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 3687-46-5, 2010, RL1

A further acute dermal toxicity study with CAS 93803-87-3 was available and used as supporting information. Based on the results of this study, the LD50 was determined to be > 2000 mg/kg bw.

Interpretation of results:

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

Conclusions:

The available data on suitable source substances did not show any toxic effects. Therefore, the target substance docosyl stearate (CAS 22413-03-2) is not considered to be hazardous following acute exposure via the dermal route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable studies (Klimisch scores 1-2). The selected studies are 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 read-across

Data on acute dermal toxicity of docosyl stearate (CAS 22413-03-2) are not available. The assessment of acute 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 22413-03-2

An acute oral toxicity study (limit test) was performed with docosyl stearate (CAS 22413-03-2) according to OECD 423 and GLP conditions (Gotemba Laboratory, 2016). In the first step 3 female Sprague-Dawley rats received a single oral gavage dose of 2000 mg/kg bw. The animals were observed for 14 days after administration. No mortality and no evidence for toxicity occurred. Based on this result, in the second step additional 3 female Sprague-Dawley rats received a single oral gavage dose of 2000 mg/kg bw and were observed for 14 days after dosing. No clinical signs and no mortality were observed in any of the animals. Necropsy revealed no substance-related findings and no effect on body weight was noted. Therefore the acute oral LD50 was found to be greater than 2000 mg/kg bw.

 

Acute dermal toxicity

CAS 3687-46-5

An acute dermal toxicity study (limit test) was performed with decyl oleate (CAS 3687-46-5) according to OECD 402 (Notox, 2010a). 2000 mg/kg bw of the test substance was applied to the skin of 5 Wistar rats/sex under an occlusive dressing for 24 hours. No mortality occurred. Clinical signs were observed in all males on Day 1 and/or 2; as piloerection (2/5 males) or chromodacryorrhoea (3/5 males). No clinical signs were noted in females. The body weight increases were within the range expected for rats used in this type of study and no treatment-related findings were reported during the necropsy and histopathological examination. Erythema (grade 1) was observed on the treated skin for up to 4 days during Day 3-7 in 4/5 females. Scales or scabs (grade 1) were noted on the treated skin area in 5/5 females and 3/5 males for up to 9 days during Day 7-15 of the observation period. The LD50 value is considered to be > 2000 mg/kg bw.

CAS 93803-87-3

The dermal effects of 2-octyldodecyl isooctadecanoate were investigated in an acute dermal toxicity GLP study performed according to OECD 402 (Notox, 1998a). In a limit test 2000 mg/kg bw of the undiluted test substance was applied to the shaved skin of 5 rats/sex for 24 h under occlusive conditions. After the exposure period, residual test substance was removed and the animals were observed for a period of 14 days. No mortality occurred. Red staining of the fur was observed in 1/5 females on Day 8 – 13. As this is a known sign of stress in rats, it was not considered to be a toxicologically relevant effect. Male and female rats showed the expected gain in body weight throughout the study. 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 read-across analogue substances indicate a very low level of acute toxicity following the oral and dermal route, as LD50 values were greater than the recommended guideline limit values. Therefore, as the available data did not identify any acute toxicity, docosyl stearate (CAS 22413-03-2) is not considered to be hazardous following acute exposure via the oral and dermal route.

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 physico-chemical, 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 docosyl stearate (CAS 22413-03-2), data will be generated from data for 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 analogue read-across approach, the available data on acute oral and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.