Isooctadecanoic acid, mixed esters with oxybis[propanediol]

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw

Read-across from analogue source substances Hexanedioic acid, mixed esters with decanoic acid, 12-hydroxyoctadecanoic acid, isostearic acid, octanoic acid, 3,3'-oxybis[1,2-propanediol] and stearic acid (CAS No. 130905-60-1), Isooctadecanoic acid, ester with oxybis[propanediol] (CAS No. 73296-86-3), 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS No. 63705-03-3) and di(isooctadecanoic) acid, diester with oxydi(propanediol) (CAS No. 67938-21-0) in a Weight-of-Evidence approach

Dermal (OECD TG 402, GLP): > 2000 mg/kg bw

Read-across from a key study with analogue source substance Isooctadecanoic acid, ester with oxybis[propanediol] (CAS No. 73296-86-3); further supported by read-across from analogue source substances Hexanedioic acid, mixed esters with decanoic acid, 12-hydroxyoctadecanoic acid, isostearic acid, octanoic acid, 3,3'-oxybis[1,2-propanediol] and stearic acid (CAS No. 130905-60-1) and 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS No. 63705-03-3)

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)

Remarks:

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

Adequacy of study:

weight of evidence

Justification for type of information:

Please refer to the Analogue Approach Justification provided in Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

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 130905-60-1, Sasol, 1990a

Additional studies and results considered in the Weight-of-Evidence approach:

CAS 73296-86-3, Lasem, 1990a: LD50 (mouse, m/f) > 5000 mg/kg bw

CAS 63705-03-3, BASF, 1988a: LD50 (rat, m/f) > 5000 mg/kg bw

CAS 67938-21-0, Clariant, 1980: LD50 (rat, f) > 5000 mg/kg bw

Interpretation of results:

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

Conclusions:

Individual LD50 values determined are > 2000 and > 5000 mg/kg bw for male and female rats and > 5000 mg/kg bw for male and female mice.

Executive summary:

The acute oral toxicity of the target substance is estimated based on adequate and reliable in vivo studies of structural analogue source substances. Individual LD50 values determined are > 2000 and > 5000 mg/kg bw for male and female rats and > 5000 mg/kg bw for male and female mice. Therefore, a LD50 value of > 2000 mg/kg bw for the target substance is considered for the hazard assessment and C&L purposes. As explained in the analogue justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the acute oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 2) studies from various source substances with similar structures and intrinsic properties. A short summary (Klimisch score 4) of a study performed with another source substance is also taken into account by means of Weight-of-Evidence. Read-across is justified based on common precursors and hydrolysis products and consistent trends in environmental fate, ecotoxicological and toxicological profile. 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 (REACH).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 Feb. - 09 March 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 February 1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

OGYEI National Institute of Pharmacy and Nutrition, H-1051 Budapest, Zrinyi u. 3, 1372 P.O. Box: 450, Hungary

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

CRL:(WI)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young healthy adults
- Weight at study initiation: 214 - 252 g
- Housing: individually in Type II polypropylen/polycarbonate cages with deep wood sawdust to allow digging
- Bedding: Lignocel 3/4-S Hygienic Animal Bedding (J. Rettenmaier & Söhne GmbH & Co. KG, D-73494 Rosenberg, Germany
- Diet: ssniff SM R/M diet (ssniff Spezialdiäten GmbH, D-59494 Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9 - 24.9
- Humidity (%): 24 - 58
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: 24 February - 9 March 2016

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back of each animal
- % coverage: approx. 10
- Treatment of test site: shaving, 24 h prior to administration
- Type of wrap if used: sterile gauze pad kept in contact with the skin using a patch with adhesive hypoallergenic plaster, the entire trunk of each animal was wrapped with a semiocclusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: residual material was removed with water of body temperature
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: a single dose of 2000 mg/kg bw of the test item was administered

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males, 5 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: on Day 0 at 1 and 5 h after application, once each day for 14 days thereafter
- Frequency of weighing: Day 0 (before administration), Days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross macroscopic examination

Preliminary study:

The test item was not expected to be lethal at 2000 mg/kg bw. A limit test with a single dose of 2000 mg/kg bw was therefore performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item did not cause mortality at the dose level of 2000 mg/kg bw.

Clinical signs:

There were no systemic clinical signs noticed in any animal throughout the study.

Body weight:

Body weight gain of all animals showed no indication of a test item-related effect.

Gross pathology:

There was no evidence of any adverse effect in the macroscopic observations.

Interpretation of results:

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

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

28 Feb - 14 Mar 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

no analytical purity reported

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted in 1981

Deviations:

yes

Remarks:

no analytical purity reported

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CFY

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna (UK) Limited, Wyton, Huntingdon, Cambridgeshire, United Kingdom
- Age at study initiation: 10 - 14 weeks
- Weight at study initiation: 201 – 225 g (males); 212 – 244 g (females)
- Housing: animals were housed in groups of 5 or 6 per sex in solid-floor polypropylene cages with sawdust bedding (except during for the 24 h exposure period)
- Diet: Rat and Mouse Expanded Diet No.1, ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 – 21
- Humidity (%): 46 – 60%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 4 cm² clipped skin of back and flanks
- % coverage: 10%
- Type of wrap if used: The test material was held in place by a piece of surgical gauze, which was semi-occluded with a double layer of elastic adhesive bandage wrapped around the trunk of the rat.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed with moist cotton wool
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for signs of toxicity and death 1 and 4 hours after dosing and subsequently at least once daily for fourteen days. Individual body weights were recorded on day 0 (day of treatment), 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

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:

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

Body weight:

Body weight gains of all dose groups were within the normal ranges in males and females during the whole study period

Gross pathology:

Necropsy examination 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.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

analytical purity not reported

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted in 1987

Deviations:

yes

Remarks:

no analytical purity reported

Qualifier:

according to guideline

Guideline:

other: EEC directive 84/449/EEC adopted in 1984

Deviations:

yes

Remarks:

no analytical purity reported

GLP compliance:

yes

Remarks:

Bezirksregierung, Lüneburg, Germany

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl: (WI) BR - Wistar, white

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, Sulzfield, Germany
- Weight at study initiation: 205 – 235 g (males); 199 – 219 g (females)
- Housing: 5 animals of the same sex per cage in Macrolon cage type III
- Diet: Ssniff-R Allendiät, pellets, ad libitum
- Water: drinking water as for human consumption supplied in drinking bottles, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 50 – 85
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 10 cm on the back of each animal
- Type of wrap if used: The test material was held in contact with the skin with a porous gauze dressing and Elastoplast R

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for clinical-toxicological signs at the following intervals after patch removal: 10 min, 1 h, 2, h, 6 h, 24 h, and thereafter once daily up to day 14. After patch removal, dermal irritation was evaluated once daily for 14 days according to a scheme based on Draize. Individual body weights were recorded immediately on day 0 (before treatment), on days 7 and 14 (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, skin reactions, necropsy

Statistics:

LD50 values were calculated according to Finney D.Y, Probit Analysis, 3rd edition, Cabridge, 1971

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:

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

Body weight:

Body weight gains of all dose groups were within the normal ranges in males and females during the whole study period

Gross pathology:

Necropsy examination 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.

Reference 4

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

08 - 24 Oct 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

LANDESANSTALT FÜR UMWELT, MESSUNGEN UND NATURSCHUTZ BADEN-WÜRTTEMBERG, Karlsruhe, Germany

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks (males), approx. 13 weeks (females)
- Weight at study initiation: 282.6 g (males), 212.4 g (females)
- Housing: the animals were housed individually in Makrolon cages, type III with bedding H 15005-29 (Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., Soest, Germany)) and environmental enrichment NGM E-022 (ABEDD® LAB & VET Service GmbH, Wien, Austria).
- Diet: VRF1(P) (SDS Special Diets Services, Altrip, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09 Oct 2012 To: 23 Oct 2012

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40 cm² clipped skin of the dorsal and dorsolateral parts of the trunk
- % coverage: ca. 10
- Type of wrap if used: the application site was covered with a semi-occlusive dressing (4 layers of absorbent gauze; Ph. Eur. (Lohmann GmbH & Co., KG)) and stretch bandage (Fixomull® Stretch (adhesive fleece) (Beiersdorf AG)).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the application site was rinsed with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.2 mL/kg bw

Duration of exposure:

24 h

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs several times on the day of administration and at least once daily thereafter each workday for the individual animals. A check for mortalities was made at least once each workday. Scoring of skin reaction according to Draize was performed 30-60 minutes after removal of the semi-occlusive dressing (after 24 h), weekly thereafter and on the last day of observation. Individual body weights were determined shortly before administration (Day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, scoring of skin reactions

Statistics:

Mean values and standard deviations of body weights were determined.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

No systemic clinical signs were observed during clinical examination.

Body weight:

The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.

Gross pathology:

No macroscopic pathologic abnormalities were noted at necropsy.

Other findings:

- Other observations: no local effects were observed in the male and female animals after administration.

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 (Klimisch score 1) key study from a source substances with similar structures and intrinsic properties. The key study is further supported by additional adequate and reliable (Klimisch score 1 and 2) studies with various analogue source substances. Read-across is justified based on common precursors and hydrolysis products and consistent trends in environmental fate, ecotoxicological and toxicological profile. The selected studies are 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 (REACH).

Additional information

Justification for read-across

The read-across from structural analogue source substances approach comprises aliphatic esters of the poly-functional alcohols di- and triglycerol. The fatty acid rests of the esters exhibit carbon chain lengths in the range C5 - C20. They are either linear and saturated in nature but also unsaturated C16 and C18 and branched C6 and C18 moieties are present. Since the alcohols employed provide 4 - 5 reactive hydroxyl functions, the esterification degree found in source and target substances ranges from mono- to penta-esters.

The available data allows for an accurate hazard and risk assessment of the target substance and the read-across concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substances by interpolation to the target substance applying the read-across concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006 (REACH). In particular, for each specific endpoint the source substances structurally closest to the target substance 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 substances are the basis of read-across. A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID section 13).

Acute oral toxicity

There are no data available regarding the acute oral toxicity of the target substance. Therefore, data obtained with various analogue source substances are considered by way of a Weight-of-Evidence approach to assess the endpoint.

An acute oral toxicity study was performed with Hexanedioic acid, mixed esters with decanoic acid, 12-hydroxyoctadecanoic acid, isostearic acid, octanoic acid, 3,3'-oxybis[1,2-propanediol] and stearic acid (CAS No. 130905-60-1) according to OECD TG 401 (Sasol, 1990a). Groups of 5 male and 5 female rats received an oral gavage dose of 2000 mg/kg bw. The animals were observed for 14 days after administration. No mortality, clinical signs or abnormal body weight changes were observed. Necropsy examination revealed no substance-related findings. Thus, the acute oral LD50 was found to be greater than 2000 mg/kg bw.

Another acute oral toxicity study was performed with 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS No. 63705-03-3) similar to OECD TG 401 (BASF, 1988a). Groups of 5 male and 5 female rats received an oral gavage dose of 5000 mg/kg bw. The animals were observed for 14 days after administration. No mortality, clinical signs or abnormal body weight changes were observed. Necropsy examination revealed no substance-related findings. Thus, the acute oral LD50 was found to be > 5000 mg/kg bw.

The acute oral toxicity of Isooctadecanoic acid, ester with oxybis[propanediol] (CAS No. 73296-86-3) was assessed in a study performed similar to OECD TG 420 which observed GLP provisions (Lasem, 1990a). As opposed to the recommendations of the TG, mice were used as test animals. 5 males and 5 females received a dose of 5000 mg/kg bw by oral gavage and observed for 14 days. No mortalities occurred and no unusual body weight changes were observed. Decreased activity was observed in one male at the 4 and 24 h observation time points and on Days 2 and 3. No other clinical signs were obvious during the study in any other animal. Terminal necropsy revealed no treatment-related findings. Therefore, the acute oral LD50 in male and female mice was determined to be > 5000 mg/kg bw.

A short study summary is available which describes the investigation of the acute oral toxicity of di(isooctadecanoic) acid, diester with oxydi(propanediol) (CAS No. 67938-21-0; Clariant, 1980). 5 female rats were administered a dose of 5000 mg/kg bw by gavage. The observation period was 14 days. No mortalities occurred and no effects on body weights were observed. 50 min after application all animals exhibited hunched posture and piloerection. 24 h after dosing all animals were free of clinical signs. No substance-related findings were reported after necropsy examinations. The acute oral LD50 in female rats was therefore established at > 5000 mg/kg bw.

The results of the four studies in the Weight-of-Evidence approach, therefore, support no or a low potential for acute oral toxicity. All LD50 values determined are > 2000 mg/kg bw.

Acute dermal toxicity

As no data regarding acute dermal toxicity of the target substance are available, assessment of this endpoint is made by read-across from the closest structural analogue substance Isooctadecanoic acid, ester with oxybis[propanediol] (CAS No. 73296-86-3). The key study is further supported by additional studies perforemd with other analogue substances. The key study followed OECD TG 402 and GLP provisions (Lonza, 2016). 5 male and 5 female rats were dermally exposed to 2000 mg/kg bw of the unchanged test substance under semi-occlusive conditions for 24 h. All animals survived the 14 days observation period and no signs of systemic toxicity as well as local skin reactions were observed. Body weight changes were not unusual and there was no evidence of any adverse effect in the macroscopic observations. In consequence, the acute dermal LD50 was found to be > 2000 mg/kg bw.

Additional information about acute dermal toxicity are provided by supporting studies. 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS No. 63705-03-3) was investigated for its acute dermal toxicity in a study according to OECD TG 402 under GLP conditions (BASF, 2012). 5 rats of each sex were exposed to a dose of 5000 mg/kg bw of the unchanged test substance for 24 h under semi-occlusive conditions. Observation for 14 days of the treated animals revealed no signs of systemic toxicity and no local skin reactions were obvious. No mortalities occurred. While the mean body weight of the male animals increased within the normal range throughout the study period, the mean body weights of the female animals did not significantly change during the first post-exposure observation week but increased during the second week within normal range. This finding was probably due to the bandage procedure. The acute dermal LD50 was therefore established to be > 5000 mg/kg bw.

There are two sudies investigating the acute dermal toxicity of Hexanedioic acid, mixed esters with decanoic acid, 12-hydroxyoctadecanoic acid, isostearic acid, octanoic acid, 3,3'-oxybis[1,2-propanediol] and stearic acid (CAS No. 130905-60-1). Both studies were performed according to OECD TG 402 and observed GLP conditions (Sasol, 1990b; Sasol, 1989). The experimental conditions were identical in both studies. 5 male and 5 female rats were dermally exposed to 2000 mg/kg bw of the unchanged test substances for 24 h under semi-occlusive conditions. All animals survived the 14 days observation periods and neither signs of systemic toxicity nor local skin effects were observed. Body weight changes were in the expected range and also terminal necropsy examinations did not reveal any treatment-related findings. The acute dermal LD50 values were therefore found to be > 2000 mg/kg bw in both studies.

Conclusion on acute toxicity

All availabale studies with adequate source substances support the absence of acute toxic effects or a very low potency of acute toxicity. All LD50 values determined are > 2000 mg/kg bw, and no signs of systemic toxicity were observed after either oral or dermal exposure. Moreover, dermal exposure did not result in local skin reactions. Based on these findings, no hazard with respect to acute oral and dermal toxicity is identified for the target substance Isooctadecanoic acid, mixed esters with oxybis[propanediol].

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 (REACH) information on intrinsic properties of substances may be generated by means other than tests, e.g. using information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI 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 read-across concept is applied to the target substance Isooctadecanoic acid, mixed esters with oxybis[propanediol], data gaps can be filled by interpolation from representative structural analogue source substances to avoid unnecessary animal testing.

The read-across concept is also used to derive the classification of the target substance taking the properties of the source substances into account. Based on the read-across concept, all available data on acute oral and dermal toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification. No data regarding acute inhalation toxicity are available.