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Administrative data

Description of key information

The toxicity of the substance is low after oral exposure. Also the toxicity after exposure via inhalation and dermal is expected to be low.

oral LD50 > 2000 mg/kg (test substance)
inhalative waiving

dermal waiving: The study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route. Additionally studies on similar substances resulted in a dermal LD50 of > 2000 mg/kg.

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:
1990-08-28 to 1990-09-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): WITAMOL 118
- Substance type: product
- Physical state: liquid
- Stability under test conditions: not mentioned
- Storage condition of test material: at temperatures below 40°C under nitrogen under a laboratory hood in the dark
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: 165 - 195 g (male); 130 - 147 g (female)
- Fasting period before study: 16 hours
- Housing: 1 - 5 animals in Makrolon cages, type III
- Diet (e.g. ad libitum): R10 Complete feed for rats ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, Haltern, Germany
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 10
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 1990-08-28 To: 1990-09-13
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.06 cm³/kg
Doses:
2000 mg/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: Examination of clinical signs up to 6 hours after the treatment and daily observations thereafter; bodyweights were determined before treatment (day 0), and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
no statistics performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
0/10 animals
Clinical signs:
none
Body weight:
reduced body weight gain of females in the second study week, normal body weight gain of male animals
Gross pathology:
no findings
Other findings:
none
Interpretation of results:
GHS criteria not met
Executive summary:

The LD50 of 1,2-Benzenedicarboxylic acid, di-C8-10-alkyl esters was greater than 2000 mg/kg bodyweight. No clinical symptoms occurred.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
from 2009-09-15 to 2009-10-13
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study, read-across
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l., San Pietro al Natisone (UD), Italy
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: 261.2 ± 11.3 g (mean weight males), 220.4 ± 4.3 g (mean weight females)
- Housing: Polycarbonate cages measuring 42.5x26.6x18 cam with stainless steel mesh lid and floor
- Diet (e.g. ad libitum): 4 RF 18 ad libitum, supplied by Mucedola S.r.l., Settimo Milanese (MI), Italy
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 15 - 25
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 2009-09-28 To: 2009-10-13
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surfaces of the trunk
- % coverage: 10 %
- Type of wrap if used: A patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, by gentle swabbing of the skin with cotton wool soaked with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Aliquots were weighed accordingly to the body weight of each animal measured prior to dosing, no further details mentioned
Duration of exposure:
24 hours
Doses:
2000 mg/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 and morbidity twice daily, clinical signs were recorded on dosing, approx. 1, 2 and 4 hours after dosing and daily thereafter, body weights were recorded on the day of allocation (day -1), days 1, 8 and 15 (day of necropsy)
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
not performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortality occurred
Clinical signs:
no clinical signs were observed
Body weight:
body weight changes were within the expected range
Gross pathology:
At necropsy examination performed on all animals at termination of the study red areas (multiple) in the thymus were noted in a single male animal. In In addition, tip of tail missing was seen in one male. No abnormalities were found in the remaining animals. No abnormalities were observed on the treated site of any animal.
Other findings:
Damaged tail was noted in a single animal prior to treatment on the day of dosing up to the end of the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute toxicity of 1,2-benzenedicarboxylic acid, C6-10 alkyl esters was investigated following dermal administration of a single dose to the rat at 2000 mg/kg.
No mortality occurred following dosing and no signs of toxicity were observed.
These results indicated that the test item has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrated the LD50 to be greater than 2000 mg/kg.
Executive summary:

The acute toxicity of 1,2 -benzenedicarboxylic acid, C6 -10 alkyl esters was investigated following dermal administration of a single dose to the rat at 2000 mg/kg according to OECD guideline 402, adopted on 24 February 1987 and Test method B.3 "Acute Toxicity (dermal)" described in Council Regulation (EC) No. 440/2008.

A single dose of 2000 mg/kg was administered to a group o 5 male and 5 female animals for 24 hours. After 14 days all animals were killed and subjected to necropsy examination. No mortality occurred following dosing and no signs of toxicity were observed. The body weight changes observed during the study were within the expected range for this species and age of animals. No significant abnormalities were found at necropsy in the animals at termination of the study. No abnormalities were observed at the treated site. These results indicated that the test item has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrated the LD50 to be greater than 2000 mg/kg.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older study conducted prior to the introduction of GLP and OECD test guidelines. Standard methods used but details of methods and results not available, read-across
Qualifier:
no guideline followed
Principles of method if other than guideline:
Rabbits given single doses of DUP of up to at least 7940 mg/kg bw. Animals observed for signs of toxicity.
GLP compliance:
no
Test type:
other:
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
No data
Duration of exposure:
No data
Doses:
Up to at least 7940 mg/kg bw
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
No data
Statistics:
No data
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 7.94 other: g/kg bw
Based on:
test mat.
Remarks on result:
other: 95% CL not caculable
Mortality:
None
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
No data
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the minimum lethal dose in rabbits for the structurally related substance Diundecyl phthalate was >7940 mg/kg bw.
Executive summary:

Acute dermal toxicity (LD50) in the rabbit for the structurally related substance Diundecyl phthalate is in excess of 7940 mg/kg body weight.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
From October 19,2009 to November 3,2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP compliant study conducted to recognised international test guidelines, read-across
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Harlan Italy S.r.l
- Age at study initiation:6/8 weeks old
- Weight at study initiation:176-200 g
- Housing: polycarbonate cages measuring 42 .5 x 26.6 x 18 cm with stainless stell mesh lid and floor
- N° of animal/cage: Individually caged (both during acclimatisation and study)
- cage try control: Daily inspected and changed as necessary (at least 3 times/week)
- Diet: 4 RF 18 (Mucedola S.r,l)
- Diet supply: ad libitum
- Water :ad libitum
- Acclimation period:5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°c +/- 2°c
- Humidity (%):55% +/- 2°C
- Air changes: 15 to 25 air changes per hour
- Photoperiod: Artificial (fluorescent tubes) , daily light/dark cycle of 12/12 hours
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure:approximately 10% of body surface
- Type of wrap if used:synthetic film

REMOVAL OF TEST SUBSTANCE
- Washing : After exposure , the adhesive bandage and gauze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water.
- Time after start of exposure:24 hours

TEST MATERIAL
- Amount(s) applied : Aliquots were weighed accordingly to the body weight of each animal measured prior dosing
- Constant volume or concentration used: yes
- Frequency of treatment: once only , on the day of dosing
- Treatment area preparation: on the day before dosing

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 male and 5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days , termination on day 15.
- Frequency of observations and weighing:days 1,8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: necropsy was carried out on all animals (gross necropsy examination for both internal and external abnormalities, with particular attention to the treatment site. All abnormalities were recorded.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None during 14 day post-exposure observation period
Clinical signs:
No abnormalities were found at necropsy examination performed on all animals at termination of the study.
Body weight:
Changes in body weight were within the expected range for this species and age of animals at the end of the study.
Gross pathology:
no pathology observed
Other findings:
None

 

 

 

 

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
The acute toxicity of the structurally related substance 1,2-benzenedicarboxylic acid, diundecyl alkyl ester was investigated following dermal administration of a single dose to the rat at 2000 mg/kg. No mortality occurred following dosing and no signs of toxicity were observed.
These results indicate that the test item, 1,2-benzenedicarboxylic acid, diundecyl alkyl ester, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.European Directives concerning the classification, packaging and labelling of dangerous substances and mixtures (Regulation (EC) no. 1907/2006, 1272/2008 and subsequent revisions) would indicate the following:

Classification : Not required
Signal word : None indicated
Hazard statement : None indicated
Executive summary:

Acute dermal of the structurally related substance Diundecyl phthalate has been investigated following administration of a single dose to the rat at a level of 2000 mg/kg. No mortality occurred, demonstrating the LD50 to be greater than 2000 mg/kg.

 

         

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies)
Reason / purpose:
data waiving: supporting information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

No mortality was observed in various studies with the target substance as well as other structurally related materials up to very high doses. Therefore the toxicity of the substance is low after oral exposure. The same is expected for inhalative and dermal toxicity.

The oral LD50 of 1,2-Benzenedicarboxylic acid, di-C8-10-alkyl esters was greater than 2000 mg/kg bodyweight. Also the studies on similar substances resulted in LD50 > 2000 m/kg.

The target substance has very low vapour pressure (ca. 0.1 Pa at 38°C), 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, and no acute inhalation test needs to be performed. Data from a supporting study on a similar substance demonstrate the lack of toxicity after single exposure via inhalation. Also data for other high molecular weight phthalates suggest that inhalation toxicity would be expected to be low (NICNAS, 2015).

No acute dermal study of the target substance is available. This endpoint is waived. The study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route.

However, in addition the acute dermal toxicity has been investigated with the source substances 1,2-Benzenedicarboxylic acid, C6-10-alkyl esters and Diundecyl phthalate following administration of a single dose to the rat at a level of 2000 mg/kg. No mortality occurred, demonstrating the LD50 to be greater than 2000 mg/kg. In the rabbit, a LD50 in excess of 7940 mg/kg body weight has been reported for the source substance Diundecyl phthalate.

On the basis of all evaluated data, the similarity of the source substances is justified on basis of similar composition, structural similarity, the physico-chemical properties, toxicokinetics and toxicological profiles and supported by various QSAR methods. Therefore the read-across approach is used to fill data gaps. There is convincing evidence that the substances have an overall common category profile in regard to this endpoints. The substances have the same basic structure (diester of 1,2-Benzenedicarboxylic acid), with almost identical and overlapping alkyl chains. All of the substances (the target substance 1,2-Benzenedicarboxylic acid, C8 -10 -alkyl esters as well as the source substance) are esters. The target substance is a mixture of different isomers, with ca. 21 % dioctyl phthalate and ca. 28 % didecyl phthalate and ca. 48 % decyl octyl phthalate. Source substance 1,2-Benzenedicarboxylic acid, C6-10-alkyl esters (CAS-number 68515-51-5), is also a mixture of different isomers, with ca. 33 % dioctyl phthalate and ca. 18 % hexyl octyl phthalate and ca. 30 % decyl octyl phthalate and ca. 7.5 % didecyl phthalate. Therefore, the isomers of the target substance are also constituents of the source substance 1. Therefore it is likely that the same is valid for the test substance.

Also data for other high molecular weight phthalates suggest that dermal toxicity would be expected to be low (NICNAS, 2015).


Justification for classification or non-classification

Overall, the acute toxicity of the test substance is expected to be low and does not require classification according to Regulation (EC) No 1272/2008.